The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the
eye of most
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
s and some
molluscs
Mollusca is the second-largest phylum of invertebrate animals after the Arthropoda, the members of which are known as molluscs or mollusks (). Around 85,000 extant species of molluscs are recognized. The number of fossil species is estim ...
. The optics of the eye create a
focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the
optic nerve
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...
to the
visual cortex
The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...
to create
visual perception
Visual perception is the ability to interpret the surrounding Biophysical environment, environment through photopic vision (daytime vision), color vision, scotopic vision (night vision), and mesopic vision (twilight vision), using light in the ...
. The retina serves a function which is in many ways analogous to that of the
film or
image sensor
An image sensor or imager is a sensor that detects and conveys information used to make an image. It does so by converting the variable attenuation of light waves (as they pass through or reflect off objects) into signals, small bursts of c ...
in a
camera
A camera is an optical instrument that can capture an image. Most cameras can capture 2D images, with some more advanced models being able to capture 3D images. At a basic level, most cameras consist of sealed boxes (the camera body), with a ...
.
The neural retina consists of several layers of
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
s interconnected by
synapses and is supported by an outer layer of pigmented epithelial cells. The primary light-sensing cells in the retina are the
photoreceptor cells, which are of two types:
rods and
cones
A cone is a three-dimensional geometric shape that tapers smoothly from a flat base (frequently, though not necessarily, circular) to a point called the apex or vertex.
A cone is formed by a set of line segments, half-lines, or lines conn ...
. Rods function mainly in dim light and provide monochromatic vision. Cones function in well-lit conditions and are responsible for the perception of colour through the use of a range of
opsins
Animal opsins are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become Retinylidene proteins, but are usually still called opsins regardless. Most p ...
, as well as high-acuity vision used for tasks such as reading. A third type of light-sensing cell, the
photosensitive ganglion cell
Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence ...
, is important for
entrainment
Entrainment may refer to:
* Air entrainment, the intentional creation of tiny air bubbles in concrete
* Brainwave entrainment, the practice of entraining one's brainwaves to a desired frequency
* Entrainment (biomusicology), the synchronization o ...
of
circadian rhythms and reflexive responses such as the
pupillary light reflex
The pupillary light reflex (PLR) or photopupillary reflex is a reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light that falls on the retinal ganglion cells of the retina in the back of the eye, ther ...
.
Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses that are sent to various visual centres of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
through the fibres of the
optic nerve
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...
. Neural signals from the rods and cones undergo processing by other neurons, whose output takes the form of
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
s in
retinal ganglion cells whose
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s form the optic nerve. Several important features of
visual perception
Visual perception is the ability to interpret the surrounding Biophysical environment, environment through photopic vision (daytime vision), color vision, scotopic vision (night vision), and mesopic vision (twilight vision), using light in the ...
can be traced to the retinal encoding and processing of light.
In vertebrate
embryonic development, the retina and the optic nerve originate as outgrowths of the developing brain, specifically the embryonic
diencephalon; thus, the retina is considered part of the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(CNS) and is actually brain tissue.
["Sensory Reception: Human Vision: Structure and function of the Human Eye" vol. 27, Encyclopædia Britannica, 1987] It is the only part of the CNS that can be visualized
noninvasively. Much like the rest of the brain is isolated from the vasular system via the
blood–brain barrier, the retina is similarly protected by the
blood–retinal barrier
The blood–retinal barrier, or the BRB, is part of the blood–ocular barrier that consists of cells that are joined tightly together to prevent certain substances from entering the tissue of the retina. It consists of non-fenestrated capillaries ...
.
Structure
Inverted versus non-inverted retina
The vertebrate retina is ''inverted'' in the sense that the light-sensing cells are in the back of the retina, so that light has to pass through layers of neurons and capillaries before it reaches the photosensitive sections of the rods and cones.
The ganglion cells, whose axons form the optic nerve, are at the front of the retina; therefore, the optic nerve must cross through the retina en route to the brain. No photoreceptors are in this region, giving rise to the
blind spot. In contrast, in the
cephalopod retina, the photoreceptors are in front, with processing neurons and capillaries behind them. Because of this, cephalopods do not have a blind spot.
Although the overlying neural tissue is partly transparent, and the accompanying
glial cell
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
s have been shown to act as
fibre-optic
An optical fiber, or optical fibre in Commonwealth English, is a flexible, transparent fiber made by drawing glass (silica) or plastic to a diameter slightly thicker than that of a human hair. Optical fibers are used most often as a means t ...
channels to transport photons directly to the photoreceptors,
light scattering
Scattering is a term used in physics to describe a wide range of physical processes where moving particles or radiation of some form, such as light or sound, are forced to deviate from a straight trajectory by localized non-uniformities (including ...
does occur.
Some vertebrates, including humans, have an area of the central retina adapted for high-acuity vision. This area, termed the
fovea centralis
The fovea centralis is a small, central pit composed of closely packed cones in the eye. It is located in the center of the macula lutea of the retina.
The fovea is responsible for sharp central vision (also called foveal vision), which is ne ...
, is avascular (does not have blood vessels), and has minimal neural tissue in front of the photoreceptors, thereby minimizing light scattering.
The cephalopods have a non-inverted retina, which is comparable in
resolving power to the eyes of many vertebrates. Squid eyes do not have an analog of the vertebrate
retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...
(RPE). Although their photoreceptors contain a protein, retinochrome, that recycles retinal and replicates one of the functions of the vertebrate RPE, cephalopod photoreceptors are likely not maintained as well as in vertebrates, and that as a result, the useful lifetime of photoreceptors in invertebrates is much shorter than in vertebrates. Having easily replaced stalk eyes (some lobsters) or retinae (some spiders, such as'' Deinopis'') rarely occurs.
The cephalopod retina does not originate as an outgrowth of the brain, as the vertebrate one does. This difference suggests that vertebrate and cephalopod eyes are not
homologous, but have evolved separately. From an evolutionary perspective, a more complex structure such as the inverted retina can generally come about as a consequence of two alternate processes - an advantageous "good" compromise between competing functional limitations, or as a historical maladaptive relic of the convoluted path of organ evolution and transformation. Vision is an important adaptation in higher vertebrates.
A third view of the "inverted" vertebrate eye is that it combines two benefits - the maintenance of the photoreceptors mentioned above, and the reduction in light intensity necessary to avoid blinding the photoreceptors, which are based on the extremely sensitive eyes of the ancestors of modern hagfish (fish that live in very deep, dark water).
Retinal layers
![Retina-diagram](https://upload.wikimedia.org/wikipedia/commons/d/d6/Retina-diagram.svg)
The vertebrate retina has 10 distinct layers. From closest to farthest from the vitreous body:
#
Inner limiting membrane
The internal limiting membrane, or inner limiting membrane, is the boundary between the retina and the vitreous body, formed by astrocytes
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astrogli ...
– basement membrane elaborated by
Müller cells Müller may refer to:
* ''Die schöne Müllerin'' (1823) (sometimes referred to as ''Müllerlieder''; ''Müllerin'' is a female miller) is a song cycle with words by Wilhelm Müller and music by Franz Schubert
* Doctor Müller, fictional character ...
#
Nerve fibre layer – axons of the
ganglion cell
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in the ...
bodies (note that a thin layer of Müller cell footplates exists between this layer and the inner limiting membrane)
#
Ganglion cell layer
The ganglion cell layer (ganglionic layer) is a layer of the retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focus ...
– contains nuclei of ganglion cells, the axons of which become the optic nerve fibres, and some displaced
amacrine cells
#
Inner plexiform layer
The inner plexiform layer is an area of the retina that is made up of a dense reticulum of fibrils formed by interlaced dendrites of retinal ganglion cells and cells of the inner nuclear layer
The inner nuclear layer or layer of inner granules, o ...
– contains the synapse between the
bipolar cell
A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smel ...
axons and the dendrites of the
ganglion and amacrine cells
#
Inner nuclear layer
The inner nuclear layer or layer of inner granules, of the retina, is made up of a number of closely packed cells, of which there are three varieties, viz.: bipolar cells, horizontal cells, and amacrine cells.
Bipolar cells
The bipolar cells, by ...
– contains the nuclei and surrounding cell bodies (perikarya) of the
amacrine cells,
bipolar cells
A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell ...
, and
horizontal cells
Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, horizo ...
#
Outer plexiform layer
The outer plexiform layer (external plexiform layer) is a layer of neuronal chemical synapse, synapses in the retina of the human eye, eye. It consists of a dense network of synapses between dendrites of horizontal cells from the inner nuclear laye ...
– projections of rods and cones ending in the rod spherule and cone pedicle, respectively, these make synapses with dendrites of bipolar cells and horizontal cells.
In the
macula
The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal av ...
r region, this is known as the ''Fiber layer of
Henle Henle can refer to:
* Friedrich Gustav Jakob Henle, a German physician, pathologist and anatomist (1809–1885)
** Loop of Henle in the kidney, named after Henle
*Fritz Henle, a photographer, known as "Mr. Rollei" for his use of the 2.25" square for ...
''.
#
Outer nuclear layer
The outer nuclear layer (or layer of outer granules or external nuclear layer), is one of the layers of the vertebrate retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates ...
– cell bodies of rods and cones
#
External limiting membrane – layer that separates the inner segment portions of the photoreceptors from their cell nuclei
# Inner segment / outer segment layer – inner segments and outer segments of rods and cones, the outer segments contain a highly specialized light-sensing apparatus.
#
Retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...
– single layer of cuboidal epithelial cells (with extrusions not shown in diagram). This layer is closest to the choroid, and provides nourishment and supportive functions to the neural retina, The black pigment melanin in the pigment layer prevents light reflection throughout the globe of the eyeball; this is extremely important for clear vision.
These layers can be grouped into four main processing stages - photoreception; transmission to
bipolar cells
A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell ...
; transmission to
ganglion cells
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in th ...
, which also contain photoreceptors, the
photosensitive ganglion cell
Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence ...
s; and transmission along the optic nerve. At each synaptic stage,
horizontal and
amacrine cells also are laterally connected.
The
optic nerve
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...
is a central tract of many axons of ganglion cells connecting primarily to the
lateral geniculate body
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral project ...
, a visual relay station in the
diencephalon (the rear of the forebrain). It also projects to the
superior colliculus, the
suprachiasmatic nucleus, and the
nucleus of the optic tract. It passes through the other layers, creating the
optic disc in primates.
Additional structures, not directly associated with vision, are found as outgrowths of the retina in some vertebrate groups. In
bird
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...
s, the
pecten is a vascular structure of complex shape that projects from the retina into the
vitreous humour
The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humor ...
; it supplies oxygen and nutrients to the eye, and may also aid in vision.
Reptiles have a similar, but much simpler, structure.
In adult humans, the entire retina is about 72% of a sphere about 22 mm in diameter. The entire retina contains about 7 million cones and 75 to 150 million rods. The optic disc, a part of the retina sometimes called "the blind spot" because it lacks photoreceptors, is located at the
optic papilla, where the optic-nerve fibres leave the eye. It appears as an oval white area of 3 mm
2. Temporal (in the direction of the temples) to this disc is the
macula
The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal av ...
, at whose centre is the
fovea
Fovea () (Latin for "pit"; plural foveae ) is a term in anatomy. It refers to a pit or depression in a structure.
Human anatomy
*Fovea centralis of the retina
* Fovea buccalis or Dimple
* Fovea of the femoral head
* Trochlear fovea of the fr ...
, a pit that is responsible for sharp central vision, but is actually less sensitive to light because of its lack of rods. Human and non-human
primate
Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians ( monkeys and apes, the latter including ...
s possess one fovea, as opposed to certain bird species, such as hawks, that are bifoviate, and dogs and cats, that possess no fovea, but a central band known as the visual streak. Around the fovea extends the central retina for about 6 mm and then the peripheral retina. The farthest edge of the retina is defined by the
ora serrata
The ora serrata is the serrated junction between the choroid and the ciliary body. This junction marks the transition from the simple, non-photosensitive area of the ciliary body to the complex, multi-layered, photosensitive region of the retina ...
. The distance from one ora to the other (or macula), the most sensitive area along the
horizontal meridian, is about 32 mm.
In section, the retina is no more than 0.5 mm thick. It has three layers of
nerve cells and two of
synapses, including the unique
ribbon synapse
The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle- calcium channel coupling th ...
. The optic nerve carries the
ganglion-cell axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s to the brain, and the blood vessels that supply the retina. The ganglion cells lie innermost in the eye while the photoreceptive cells lie beyond. Because of this counter-intuitive arrangement, light must first pass through and around the ganglion cells and through the thickness of the retina, (including its capillary vessels, not shown) before reaching the rods and cones. Light is absorbed by the
retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...
or the
choroid (both of which are opaque).
The
white blood cells in the
capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
in front of the photoreceptors can be perceived as tiny bright moving dots when looking into blue light. This is known as the
blue field entoptic phenomenon
The blue field entoptic phenomenon is an entoptic phenomenon characterized by the appearance of tiny bright dots (nicknamed blue-sky sprites) moving quickly along squiggly lines in the visual field, especially when looking into bright blue light ...
(or Scheerer's phenomenon).
Between the
ganglion-cell layer and the rods and cones are two layers of
neuropil
Neuropil (or "neuropile") is any area in the nervous system composed of mostly unmyelinated axons, dendrites and glial cell processes that forms a synaptically dense region containing a relatively low number of cell bodies. The most prevalent an ...
s, where synaptic contacts are made. The neuropil layers are the
outer plexiform layer
The outer plexiform layer (external plexiform layer) is a layer of neuronal chemical synapse, synapses in the retina of the human eye, eye. It consists of a dense network of synapses between dendrites of horizontal cells from the inner nuclear laye ...
and the
inner plexiform layer
The inner plexiform layer is an area of the retina that is made up of a dense reticulum of fibrils formed by interlaced dendrites of retinal ganglion cells and cells of the inner nuclear layer
The inner nuclear layer or layer of inner granules, o ...
. In the outer neuropil layer, the rods and cones connect to the vertically running
bipolar cells
A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell ...
, and the horizontally oriented
horizontal cells
Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, horizo ...
connect to ganglion cells.
The central retina predominantly contains cones, while the peripheral retina predominantly contains rods. In total, the retina has about seven million cones and a hundred million rods. At the centre of the macula is the foveal pit where the cones are narrow and long, and arranged in a hexagonal
mosaic
A mosaic is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and were particularly pop ...
, the most dense, in contradistinction to the much fatter cones located more peripherally in the retina.
At the foveal pit, the other retinal layers are displaced, before building up along the foveal slope until the rim of the fovea, or
parafovea Parafovea or the parafoveal belt is a region in the retina that circumscribes the fovea and is part of the macula lutea. It is circumscribed by the perifovea.
Effect on reading
In reading, information within 1° (approximately 6–8 characters ...
, is reached, which is the thickest portion of the retina. The macula has a yellow pigmentation, from screening pigments, and is known as the macula lutea. The area directly surrounding the fovea has the highest density of rods converging on single bipolar cells. Since its cones have a much lesser convergence of signals, the fovea allows for the sharpest vision the eye can attain.
Though the rod and cones are a
mosaic
A mosaic is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and were particularly pop ...
of sorts, transmission from receptors, to bipolars, to
ganglion cells
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in th ...
is not direct. Since about 150 million receptors and only 1 million optic nerve fibres exist, convergence and thus mixing of signals must occur. Moreover, the horizontal action of the
horizontal and
amacrine cells can allow one area of the retina to control another (e.g. one stimulus inhibiting another). This inhibition is key to lessening the sum of messages sent to the higher regions of the brain. In some lower vertebrates (e.g. the
pigeon
Columbidae () is a bird family consisting of doves and pigeons. It is the only family in the order Columbiformes. These are stout-bodied birds with short necks and short slender bills that in some species feature fleshy ceres. They primarily ...
), control of messages is "centrifugal" – that is, one layer can control another, or higher regions of the brain can drive the retinal nerve cells, but in primates, this does not occur.
Layers imagable with optical coherence tomography
Using
optical coherence tomography
Optical coherence tomography (OCT) is an imaging technique that uses low-coherence light to capture micrometer-resolution, two- and three-dimensional images from within optical scattering media (e.g., biological tissue). It is used for medica ...
(OCT), 18 layers can be identified in the retina. The layers and anatomical correlation are:
![Macula Histology OCT](https://upload.wikimedia.org/wikipedia/commons/a/ad/Macula_Histology_OCT.jpg)
From innermost to outermost, the layers identifiable by OCT are as follows:
Development
Retinal development begins with the establishment of the eye fields mediated by the
SHH and
SIX3
Homeobox protein SIX3 is a protein that in humans is encoded by the ''SIX3'' gene.
Function
The SIX homeobox 3 (SIX3) gene is crucial in embryonic development by providing necessary instructions for the formation of the forebrain and eye deve ...
proteins, with subsequent development of the optic vesicles regulated by the
PAX6
Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene.
Function
PAX6 is a member of the Pax gene family which is responsible for carrying the geneti ...
and
LHX2
LIM/homeobox protein Lhx2 is a protein that in humans is encoded by the ''LHX2'' gene.
This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encod ...
proteins.
The role of Pax6 in eye development was elegantly demonstrated by Walter Gehring and colleagues, who showed that ectopic expression of Pax6 can lead to eye formation on
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
antennae, wings, and legs. The optic vesicle gives rise to three structures: the neural retina, the retinal pigmented epithelium, and the optic stalk. The neural retina contains the retinal progenitor cells (RPCs) that give rise to the seven cell types of the retina. Differentiation begins with the
retinal ganglion cells and concludes with production of the Muller glia. Although each cell type differentiates from the RPCs in a sequential order, there is considerable overlap in the timing of when individual cell types differentiate.
The cues that determine a RPC daughter cell fate are coded by multiple transcription factor families including the
bHLH and
homeodomain
A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full ...
factors.
In addition to guiding cell fate determination, cues exist in the retina to determine the dorsal-ventral (D-V) and nasal-temporal (N-T) axes. The D-V axis is established by a ventral to dorsal gradient of
VAX2
VAX (an acronym for Virtual Address eXtension) is a series of computers featuring a 32-bit computing, 32-bit instruction set architecture (ISA) and virtual memory that was developed and sold by Digital Equipment Corporation (DEC) in the late 20 ...
, whereas the N-T axis is coordinated by expression of the forkhead transcription factors
FOXD1
Forkhead box D1 is a protein that in humans is encoded by the FOXD1 gene. Forkhead d1 is a kidney expressed transcription factor maps at the chromosome 5 at position 5q12—q13, identified in ''Drosophila forkhead'' protein and mammalian HNF3 tra ...
and
FOXG1
Forkhead box protein G1 is a protein that in humans is encoded by the ''FOXG1'' gene.
Function
This gene belongs to the forkhead family of transcription factors that is characterized by a distinct forkhead domain. The complete function of thi ...
. Additional gradients are formed within the retina.
This spatial distribution may aid in proper targeting of RGC axons that function to establish the retinotopic map.
Blood supply
![Fundus photograph of normal right eye](https://upload.wikimedia.org/wikipedia/commons/3/37/Fundus_photograph_of_normal_right_eye.jpg)
The retina is stratified into distinct layers, each containing specific cell types or cellular compartments that have metabolisms with different nutritional requirements. To satisfy these requirements, the
ophthalmic artery
The ophthalmic artery (OA) is an artery of the head. It is the first branch of the internal carotid artery distal to the cavernous sinus. Branches of the ophthalmic artery supply all the structures in the orbit around the eye, as well as some s ...
bifurcates and supplies the retina via two distinct vascular networks: the choroidal network, which supplies the choroid and the outer retina, and the retinal network, which supplies the retina's inner layer.
Circulatory mechanisms
At first glance, one may think that the vertebrate retina is "wired wrongly" or "badly designed"; but in fact, the retina could not function if it were not inverted. The photoreceptor layer must be embedded in the retinal pigment epithelium (RPE), which performs at least seven vital functions, one of the most obvious being to supply oxygen and other necessary nutrients needed for the photoreceptors to function. These nutrients include glucose, fatty acids, and retinal. The mammalian photoreceptor amplification process uses large quantities energy for vision in photopic conditions (requiring less under scotopic conditions) and, thus, requires the large supply nutrients supplied by the blood vessels in the choroid, which lies beyond the RPE. The choroid supplies about 75% of these nutrients to the retina and the retinal vasculature only 25%.
When light strikes 11-cis-retinal (in the disks in the rods and cones), 11-cis-retinal changes to all-trans-retinal which then triggers changes in the opsins. Now, the outer segments do not regenerate the retinal back into the cis- form once it has been changed by light. Instead the retinal is pumped out to the surrounding RPE where it is regenerated and transported back into the outer segments of the photoreceptors. This recycling function of the RPE protects the photoreceptors against photo-oxidative damage and allows the photoreceptor cells to have decades-long useful lives.
In birds
The bird retina is devoid of blood vessels, perhaps to give unobscured passage of light for forming images, thus giving better resolution. It is, therefore, a considered view that the bird retina depends for nutrition and oxygen supply on a specialized organ, called the "pecten" or
pecten oculi
The pecten or pecten oculi is a comb-like structure of blood vessels belonging to the choroid in the eye of a bird. It is a non- sensory, pigmented structure that projects into the vitreous humor from the point where the optic nerve enters the ...
, located on the blind spot or optic disk. This organ is extremely rich in blood vessels and is thought to supply nutrition and oxygen to the bird retina by diffusion through the vitreous body. The pecten is highly rich in alkaline phosphatase activity and polarized cells in its bridge portion – both befitting its secretory role. Pecten cells are packed with dark melanin granules, which have been theorized to keep this organ warm with the absorption of stray light falling on the pecten. This is considered to enhance metabolic rate of the pecten, thereby exporting more nutritive molecules to meet the stringent energy requirements of the retina during long periods of exposure to light.
Biometric identification and diagnosis of disease
The bifurcations and other physical characteristics of the inner retinal vascular network are known to vary among individuals,
and these individual variances have been used for
biometric identification
Biometrics are body measurements and calculations related to human characteristics. Biometric authentication (or realistic authentication) is used in computer science as a form of identification and access control. It is also used to identify in ...
and for early detection of the onset of disease. The mapping of vascular bifurcations is one of the basic steps in biometric identification.
Results of such analyses of retinal blood vessel structure can be evaluated against the ground truth data of vascular bifurcations of retinal fundus images that are obtained from the DRIVE dataset. In addition, the classes of vessels of the DRIVE dataset have also been identified,
and an automated method for accurate extraction of these bifurcations is also available.
Changes in retinal blood circulation are seen with aging and exposure to air pollution,
and may indicate cardiovascular diseases such as hypertension and atherosclerosis.
Determining the equivalent width of arterioles and venules near the optic disc is also a widely used technique to identify cardiovascular risks.
Function
The retina translates an optical image into neural impulses starting with the patterned excitation of the colour-sensitive pigments of its rods and cones, the retina's
photoreceptor cells. The excitation is processed by the neural system and various parts of the brain working in parallel to form a representation of the external environment in the brain.
The cones respond to bright light and mediate high-resolution colour vision during daylight illumination (also called
photopic vision
Photopic vision is the vision of the eye under well-lit conditions (luminance levels from 10 to 108 cd/m2). In humans and many other animals, photopic vision allows color perception, mediated by cone cells, and a significantly higher visu ...
). The rod responses are saturated at daylight levels and don't contribute to pattern vision. However, rods do respond to dim light and mediate lower-resolution, monochromatic vision under very low levels of illumination (called
scotopic vision
In the study of human visual perception, scotopic vision (or scotopia) is the vision of the eye under low-light conditions. The term comes from Greek ''skotos'', meaning "darkness", and ''-opia'', meaning "a condition of sight". In the human eye, ...
). The illumination in most office settings falls between these two levels and is called
mesopic vision
Mesopic vision, sometimes also called twilight vision, is a combination of photopic and scotopic vision under low-light (but not necessarily dark) conditions. Mesopic levels range approximately from 0.01 to 3.0 cd/m2 in luminance. Most ni ...
. At mesopic light levels, both the rods and cones are actively contributing pattern information. What contribution the rod information makes to pattern vision under these circumstances is unclear.
The response of cones to various wavelengths of light is called their spectral sensitivity. In normal human vision, the spectral sensitivity of a cone falls into one of three subtypes, often called blue, green, and red, but more accurately known as short, medium, and long wavelength-sensitive cone subtypes. It is a lack of one or more of the cone subtypes that causes individuals to have deficiencies in colour vision or various kinds of
colour blindness. These individuals are not blind to objects of a particular colour, but are unable to distinguish between colours that can be distinguished by people with normal vision. Humans have this
trichromatic vision
Trichromacy or trichromatism is the possessing of three independent channels for conveying color information, derived from the three different types of cone cells in the eye. Organisms with trichromacy are called trichromats.
The normal exp ...
, while most other mammals lack cones with red sensitive pigment and therefore have poorer dichromatic colour vision. However, some animals have four spectral subtypes, e.g. the trout adds an ultraviolet subgroup to short, medium, and long subtypes that are similar to humans. Some fish are sensitive to the polarization of light as well.
In the photoreceptors, exposure to light hyperpolarizes the membrane in a series of graded shifts. The outer cell segment contains a
photopigment
Photopigments are unstable pigments that undergo a chemical change when they absorb light. The term is generally applied to the non-protein chromophore moiety of photosensitive chromoproteins, such as the pigments involved in photosynthesis and pho ...
. Inside the cell the normal levels of
cyclic guanosine monophosphate
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in r ...
(cGMP) keep the Na+ channel open, and thus in the resting state the cell is depolarised. The
photon
A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they a ...
causes the
retinal
Retinal (also known as retinaldehyde) is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).
Some microorganisms use reti ...
bound to the receptor protein to
isomerise to
trans-retinal. This causes the receptor to activate multiple
G-protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
s. This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, resulting in the closing of Na+
cyclic nucleotide-gated ion channel
Cycle, cycles, or cyclic may refer to:
Anthropology and social sciences
* Cyclic history, a theory of history
* Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr.
* Social cycle, various cycles in so ...
s (CNGs). Thus the cell is hyperpolarised. The amount of neurotransmitter released is reduced in bright light and increases as light levels fall. The actual photopigment is bleached away in bright light and only replaced as a chemical process, so in a transition from bright light to darkness the eye can take up to thirty minutes to reach full sensitivity.
When thus excited by light, the photoceptor sends a proportional response
synaptically to
bipolar cell
A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smel ...
s which in turn signal the
retinal ganglion cells. The photoreceptors are also cross-linked by
horizontal cell
Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, hori ...
s and
amacrine cell
Amacrine cells are interneurons in the retina. They are named from the Greek roots ''a–'' ("non"), ''makr–'' ("long") and ''in–'' ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they proj ...
s, which modify the synaptic signal before it reaches the ganglion cells, the neural signals being intermixed and combined. Of the retina's nerve cells, only the retinal ganglion cells and few amacrine cells create
action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
s.
In the retinal ganglion cells there are two types of response, depending on the
receptive field
The receptive field, or sensory space, is a delimited medium where some physiological stimuli can evoke a sensory neuronal response in specific organisms.
Complexity of the receptive field ranges from the unidimensional chemical structure of o ...
of the cell. The receptive fields of retinal ganglion cells comprise a central, approximately circular area, where light has one effect on the firing of the cell, and an annular surround, where light has the opposite effect. In ON cells, an increment in light intensity in the centre of the receptive field causes the firing rate to increase. In OFF cells, it makes it decrease. In a linear model, this response profile is well described by a
difference of Gaussians In imaging science, difference of Gaussians (DoG) is a feature enhancement algorithm that involves the subtraction of one Gaussian blurred version of an original image from another, less blurred version of the original. In the simple case of grays ...
and is the basis for
edge detection
Edge detection includes a variety of mathematical methods that aim at identifying edges, curves in a digital image at which the image brightness changes sharply or, more formally, has discontinuities. The same problem of finding discontinuitie ...
algorithms. Beyond this simple difference, ganglion cells are also differentiated by chromatic sensitivity and the type of spatial summation. Cells showing linear spatial summation are termed X cells (also called parvocellular, P, or midget ganglion cells), and those showing non-linear summation are Y cells (also called magnocellular, M, or parasol retinal ganglion cells), although the correspondence between X and Y cells (in the cat retina) and P and M cells (in the primate retina) is not as simple as it once seemed.
In the transfer of visual signals to the brain, the
visual pathway, the retina is vertically divided in two, a temporal (nearer to the temple) half and a nasal (nearer to the nose) half. The axons from the nasal half cross the brain at the
optic chiasma
In neuroanatomy, the optic chiasm, or optic chiasma (; , ), is the part of the brain where the optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus. The optic chiasm is found in all vertebrate ...
to join with axons from the temporal half of the other eye before passing into the
lateral geniculate body
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral project ...
.
Although there are more than 130 million retinal receptors, there are only approximately 1.2 million fibres (axons) in the optic nerve. So, a large amount of pre-processing is performed within the retina. The
fovea
Fovea () (Latin for "pit"; plural foveae ) is a term in anatomy. It refers to a pit or depression in a structure.
Human anatomy
*Fovea centralis of the retina
* Fovea buccalis or Dimple
* Fovea of the femoral head
* Trochlear fovea of the fr ...
produces the most accurate information. Despite occupying about 0.01% of the visual field (less than 2° of
visual angle
Visual angle is the angle a viewed object subtends at the eye, usually stated in degrees of arc.
It also is called the object's angular size.
The diagram on the right shows an observer's eye looking at a frontal extent (the vertical arrow) tha ...
), about 10% of axons in the optic nerve are devoted to the fovea. The resolution limit of the fovea has been determined to be around 10,000 points. The information capacity is estimated at 500,000 bits per second (for more information on bits, see
information theory) without colour or around 600,000 bits per second including colour.
Spatial encoding
![Receptive field](https://upload.wikimedia.org/wikipedia/commons/1/16/Receptive_field.png)
When the retina sends neural impulses representing an image to the brain, it spatially encodes (compresses) those impulses to fit the limited capacity of the optic nerve. Compression is necessary because there are 100 times more
photoreceptor cells than
ganglion cell
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in the ...
s. This is done by "
decorrelation
Decorrelation is a general term for any process that is used to reduce autocorrelation within a signal, or cross-correlation within a set of signals, while preserving other aspects of the signal. A frequently used method of decorrelation is the u ...
", which is carried out by the "centre–surround structures", which are implemented by the bipolar and ganglion cells.
There are two types of centre–surround structures in the retina – on-centres and off-centres. On-centres have a positively weighted centre and a negatively weighted surround. Off-centres are just the opposite. Positive weighting is more commonly known as
excitatory
In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...
, and negative weighting as
inhibitory
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...
.
These centre–surround structures are not physical apparent, in the sense that one cannot see them by staining samples of tissue and examining the retina's anatomy. The centre–surround structures are logical (i.e., mathematically abstract) in the sense that they depend on the connection strengths between bipolar and ganglion cells. It is believed that the connection strength between cells is caused by the number and types of
ion channels embedded in the
synapses between the bipolar and ganglion cells.
The centre–surround structures are mathematically equivalent to the
edge detection
Edge detection includes a variety of mathematical methods that aim at identifying edges, curves in a digital image at which the image brightness changes sharply or, more formally, has discontinuities. The same problem of finding discontinuitie ...
algorithms used by computer programmers to extract or enhance the edges in a digital photograph. Thus, the retina performs operations on the image-representing impulses to enhance the edges of objects within its visual field. For example, in a picture of a dog, a cat and a car, it is the edges of these objects that contain the most information. In order for higher functions in the brain (or in a computer for that matter) to extract and classify objects such as a dog and a cat, the retina is the first step to separating out the various objects within the scene.
As an example, the following
matrix
Matrix most commonly refers to:
* ''The Matrix'' (franchise), an American media franchise
** ''The Matrix'', a 1999 science-fiction action film
** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchis ...
is at the heart of a computer
algorithm
In mathematics and computer science, an algorithm () is a finite sequence of rigorous instructions, typically used to solve a class of specific problems or to perform a computation. Algorithms are used as specifications for performing ...
that implements edge detection. This matrix is the computer equivalent to the centre–surround structure. In this example, each box (element) within this matrix would be connected to one photoreceptor. The photoreceptor in the centre is the current receptor being processed. The centre photoreceptor is multiplied by the +1 weight factor. The surrounding photoreceptors are the "nearest neighbors" to the centre and are multiplied by the −1/8 value. The sum of all nine of these elements is finally calculated. This summation is repeated for every photoreceptor in the image by shifting left to the end of a row and then down to the next line.
The total sum of this matrix is zero, if all the inputs from the nine photoreceptors are of the same value. The zero result indicates the image was uniform (non-changing) within this small patch. Negative or positive sums mean the image was varying (changing) within this small patch of nine photoreceptors.
The above matrix is only an approximation to what really happens inside the retina. The differences are:
* The above example is called "balanced". The term balanced means that the sum of the negative weights is equal to the sum of the positive weights so that they cancel out perfectly. Retinal ganglion cells are almost never perfectly balanced.
* The table is square while the centre–surround structures in the retina are circular.
* Neurons operate on
spike train
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...
s traveling down nerve cell
axons. Computers operate on a single
floating-point number
In computing, floating-point arithmetic (FP) is arithmetic that represents real numbers approximately, using an integer with a fixed precision, called the significand, scaled by an integer exponent of a fixed base. For example, 12.345 can be r ...
that is essentially constant from each input
pixel
In digital imaging, a pixel (abbreviated px), pel, or picture element is the smallest addressable element in a raster image, or the smallest point in an all points addressable display device.
In most digital display devices, pixels are the ...
. (The computer pixel is basically the equivalent of a biological photoreceptor.)
* The retina performs all these calculations in parallel while the computer operates on each pixel one at a time. The retina performs no repeated summations and shifting as would a computer.
* Finally, the
horizontal and
amacrine cell
Amacrine cells are interneurons in the retina. They are named from the Greek roots ''a–'' ("non"), ''makr–'' ("long") and ''in–'' ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they proj ...
s play a significant role in this process, but that is not represented here.
Here is an example of an input image and how edge detection would modify it.
![Edge-detection-2](https://upload.wikimedia.org/wikipedia/commons/6/62/Edge-detection-2.jpg)
Once the image is spatially encoded by the centre–surround structures, the signal is sent out along the optic nerve (via the axons of the ganglion cells) through the
optic chiasm
In neuroanatomy, the optic chiasm, or optic chiasma (; , ), is the part of the brain where the optic nerves cross. It is located at the bottom of the brain immediately inferior to the hypothalamus. The optic chiasm is found in all vertebrat ...
to the LGN (
lateral geniculate nucleus
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral projec ...
). The exact function of the LGN is unknown at this time. The output of the LGN is then sent to the back of the brain. Specifically, the output of the LGN "radiates" out to the V1
primary visual cortex
The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...
.
Simplified signal flow: Photoreceptors → Bipolar → Ganglion → Chiasm → LGN → V1 cortex
Clinical significance
There are many inherited and acquired diseases or disorders that may affect the retina. Some of them include:
*
Retinitis pigmentosa
Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...
is a group of genetic diseases that affect the retina and cause the loss of night vision and peripheral vision.
*
Macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
describes a group of diseases characterized by loss of central vision because of death or impairment of the cells in the
macula
The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal av ...
.
*
Cone-rod dystrophy
A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.
Presentation
The most common symptoms of cone dystrophy are vision loss (age of onset r ...
(CORD) describes a number of diseases where vision loss is caused by deterioration of the
cones
A cone is a three-dimensional geometric shape that tapers smoothly from a flat base (frequently, though not necessarily, circular) to a point called the apex or vertex.
A cone is formed by a set of line segments, half-lines, or lines conn ...
and/or
rods in the retina.
* In
retinal separation, the retina detaches from the back of the eyeball.
Ignipuncture Ignipuncture (Latin: ''Ignis'' (fire) + ''puncture'') is the procedure of closing a retinal separation by transfixation of the break via cauterization
Cauterization (or cauterisation, or cautery) is a medical practice or technique of burning a p ...
is an outdated treatment method. The term
retinal detachment is used to describe a separation of the neurosensory retina from the
retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...
.
There are several modern treatment methods for fixing a retinal detachment:
pneumatic retinopexy,
scleral buckle
A scleral buckle is one of several ophthalmologic procedures that can be used to repair a retinal detachment. Retinal detachments are usually caused by retinal tears, and a scleral buckle can be used to close the retinal break, both for acute and ...
,
cryotherapy
Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
,
laser photocoagulation
Laser coagulation or laser photocoagulation surgery is used to treat a number of eye diseases and has become widely used in recent decades. During the procedure, a laser is used to finely cauterize ocular blood vessels to attempt to bring about var ...
and pars plana
vitrectomy
Vitrectomy is a surgery to remove some or all of the vitreous humor from the eye.
Anterior vitrectomy entails removing small portions of the vitreous humor from the front structures of the eye—often because these are tangled in an intraocular ...
.
* Both
hypertension and
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
can cause damage to the tiny blood vessels that supply the retina, leading to
hypertensive retinopathy
Hypertensive retinopathy is damage to the retina and retinal circulation due to high blood pressure (i.e. hypertension).
Signs and symptoms
Most patients with hypertensive retinopathy have no symptoms. However, some may report decreased or blurr ...
and
diabetic retinopathy
Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries.
Diabetic retinopathy affects up to 80 perc ...
.
*
Retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively fo ...
is a
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
of the retina.
* Retinal diseases in
dog
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
s include
retinal dysplasia
Retinal dysplasia is an eye disease affecting the retina of animals and, less commonly, humans. It is usually a nonprogressive disease and can be caused by viral infections, drugs, vitamin A deficiency, or genetic defects. Retinal dysplasia i ...
,
progressive retinal atrophy, and
sudden acquired retinal degeneration.
* ''
Lipaemia retinalis'' is a white appearance of the retina, and can occur by lipid deposition in
lipoprotein lipase deficiency.
* ''
Retinal Detachment''. The neural retina occasionally detaches from the pigment epithelium. In some instances, the cause of such detachment is injury to the eyeball that allows fluid or blood to collect between the neural retina and the pigment epithelium. Detachment is occasionally caused by contracture of fine collagenous fibrils in the vitreous humor, which pull areas of the retina toward the interior of the globe.
* ''
Night blindness
Nyctalopia (; ), also called night-blindness, is a condition making it difficult or impossible to see in relatively low light. It is a symptom of several eye diseases. Night blindness may exist from birth, or be caused by injury or malnutrition ...
'': Night blindness occurs in any person with severe vitamin A deficiency. The reason for this is that without vitamin A, the amounts of retinal and rhodopsin that can be formed are severely depressed. This condition is called night blindness because the amount of light available at night is too little to permit adequate vision in vitamin A–deficient persons.
In addition, the retina has been described as a "window" into the brain and body, given that abnormalities detected through an examination of the retina can discover both neurological and systemic diseases.
Diagnosis
A number of different instruments are available for the diagnosis of diseases and disorders affecting the retina.
Ophthalmoscopy
Ophthalmoscopy, also called funduscopy, is a test that allows a health professional to see inside the fundus of the eye and other structures using an ophthalmoscope (or funduscope). It is done as part of an eye examination and may be done as part ...
and
fundus photography
Fundus photography involves photographing the rear of an eye, also known as the fundus. Specialized fundus cameras consisting of an intricate microscope attached to a flash enabled camera are used in fundus photography. The main structures that ...
have long been used to examine the retina. Recently,
adaptive optics
Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effect of incoming wavefront distortions by deforming a mirror in order to compensate for the distortion. It is used in astronomical tele ...
has been used to image individual rods and cones in the living human retina, and a company based in Scotland has engineered technology that allows physicians to observe the complete retina without any discomfort to patients.
The
electroretinogram
Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors ( rods and cones), inner retinal cells ( bipolar and amacrine cells), and the ganglion cells. Electrodes are placed on th ...
is used to
non-invasively measure the retina's electrical activity, which is affected by certain diseases. A relatively new technology, now becoming widely available, is
optical coherence tomography
Optical coherence tomography (OCT) is an imaging technique that uses low-coherence light to capture micrometer-resolution, two- and three-dimensional images from within optical scattering media (e.g., biological tissue). It is used for medica ...
(OCT). This non-invasive technique allows one to obtain a
3D volumetric or high resolution cross-sectional
tomogram
Tomography is imaging by sections or sectioning that uses any kind of penetrating wave. The method is used in radiology, archaeology, biology, atmospheric science, geophysics, oceanography, plasma physics, materials science, astrophysics, quantu ...
of the fine structures of the retina, with
histologic
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
quality.
Retinal vessel analysis is a non-invasive method to examine the small arteries and veins in the retina which allows to draw conclusions about the morphology and the function of small vessels elsewhere in the human body. It has been established as a predictor of
cardiovascular disease and seems to have, according to a study published in 2019, potential in the early detection of Alzheimer's disease.
Treatment
Treatment depends upon the nature of the disease or disorder.
Common treatment modalities
The following are commonly modalities of management for retinal disease:
*
Intravitreal
Intravitreal is a route of administration of a drug, or other substance, in which the substance is delivered into the vitreous humor of the eye. "Intravitreal" literally means "inside an eye". Intravitreal injections were first introduced in 1911 ...
medication, such as
anti-VEGF or
corticosteroid agents
*
Vitreoretinal surgery
Eye surgery, also known as ophthalmic or ocular surgery, is surgery performed on the eye or its adnexa, by an ophthalmologist or sometimes, an optometrist. Eye surgery is synonymous with ophthalmology. The eye is a very fragile organ, and r ...
* Use of nutritional supplements
* Modification of systemic risk factors for retinal disease
Uncommon treatment modalities
Retinal gene therapy
Gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
holds promise as a potential avenue to cure a wide range of retinal diseases. This involves using a non-infectious virus to shuttle a gene into a part of the retina. Recombinant
adeno-associated virus
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in di ...
(rAAV) vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. rAAV vectors are increasingly utilized for their ability to mediate efficient transduction of
retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...
(RPE),
photoreceptor cells
A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...
and
retinal ganglion cells
A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina ...
. Each cell type can be specifically targeted by choosing the appropriate combination of AAV
serotype, promoter, and intraocular injection site.
Several clinical trials have already reported positive results using rAAV to treat
Leber's congenital amaurosis
Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.
It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be co ...
, showing that the therapy was both safe and effective.
There were no serious adverse events, and patients in all three studies showed improvement in their visual function as measured by a number of methods. The methods used varied among the three trials, but included both functional methods such as visual acuity
and functional mobility
as well as objective measures that are less susceptible to bias, such as the pupil's ability to respond to light
and improvements on functional MRI.
Improvements were sustained over the long-term, with patients continuing to do well after more than 1.5 years.
The unique architecture of the retina and its relatively immune-privileged environment help this process.
Tight junction
Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
s that form the
blood retinal barrier separate the subretinal space from the blood supply, thus protecting it from microbes and most immune-mediated damage, and enhancing its potential to respond to vector-mediated therapies. The highly compartmentalized anatomy of the eye facilitates accurate delivery of therapeutic vector suspensions to specific tissues under direct visualization using microsurgical techniques. In the sheltered environment of the retina, AAV vectors are able to maintain high levels of
transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change th ...
expression in the retinal pigmented epithelium (RPE), photoreceptors, or ganglion cells for long periods of time after a single treatment. In addition, the eye and the visual system can be routinely and easily monitored for visual function and retinal structural changes after injections with noninvasive advanced technology, such as visual acuities,
contrast sensitivity
Contrast is the contradiction in luminance or colour that makes an object (or its representation in an image or display) distinguishable. In visual perception of the real world, contrast is determined by the difference in the colour and bright ...
,
fundus auto-fluorescence (FAF), dark-adapted visual thresholds, vascular diameters, pupillometry,
electroretinography
Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors ( rods and cones), inner retinal cells ( bipolar and amacrine cells), and the ganglion cells. Electrodes are placed on th ...
(ERG), multifocal ERG and
optical coherence tomography
Optical coherence tomography (OCT) is an imaging technique that uses low-coherence light to capture micrometer-resolution, two- and three-dimensional images from within optical scattering media (e.g., biological tissue). It is used for medica ...
(OCT).
This strategy is effective against a number of retinal diseases that have been studied, including neovascular diseases that are features of
age-related macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
,
diabetic retinopathy
Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries.
Diabetic retinopathy affects up to 80 perc ...
and
retinopathy of prematurity
Retinopathy of prematurity (ROP), also called retrolental fibroplasia (RLF) and Terry syndrome, is a disease of the eye affecting prematurely born babies generally having received neonatal intensive care, in which oxygen therapy is used due to ...
. Since the regulation of vascularization in the mature retina involves a balance between endogenous positive
growth factors
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for reg ...
, such as
vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
(VEGF) and inhibitors of
angiogenesis, such as pigment epithelium-derived factor (
PEDF
Pigment epithelium-derived factor (PEDF) also known as serpin F1 (SERPINF1), is a multifunctional secreted protein that has anti-angiogenic, anti-tumorigenic, and neurotrophic functions. Found in vertebrates, this 50 kDa protein is being researc ...
), rAAV-mediated expression of PEDF, angiostatin, and the soluble VEGF receptor sFlt-1, which are all antiangiogenic proteins, have been shown to reduce aberrant vessel formation in animal models.
Since specific gene therapies cannot readily be used to treat a significant fraction of patients with retinal dystrophy, there is a major interest in developing a more generally applicable survival factor therapy.
Neurotrophic factors
Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their trop ...
have the ability to modulate neuronal growth during development to maintain existing cells and to allow recovery of injured neuronal populations in the eye. AAV encoding neurotrophic factors such as fibroblast growth factor (FGF) family members and GDNF either protected photoreceptors from apoptosis or slowed down cell death.
Organ transplantation
Transplantation of retinas has been attempted, but without much success. At
MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
, The University of Southern California, RWTH Aachen University, and the
University of New South Wales
The University of New South Wales (UNSW), also known as UNSW Sydney, is a public research university based in Sydney, New South Wales, Australia. It is one of the founding members of Group of Eight, a coalition of Australian research-intensiv ...
, an "artificial retina" is under development: an implant which will bypass the photoreceptors of the retina and stimulate the attached nerve cells directly, with signals from a digital camera.
History
Around 300
BCE
Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the or ...
,
Herophilos
Herophilos (; grc-gre, Ἡρόφιλος; 335–280 BC), sometimes Latinised Herophilus, was a Greek physician regarded as one of the earliest anatomists. Born in Chalcedon, he spent the majority of his life in Alexandria. He was the first sci ...
identified the retina from dissections of cadaver eyes. He called it the ''arachnoid'' layer, from its resemblance to a spider web, and ''retiform'', from its resemblance to a casting net. The term
arachnoid
Arachnoid may refer to:
* Relating to arachnids
* Arachnoid (astrogeology), a geological structure found only on the planet Venus
* Arachnoid (botany), referring to organs with a cobwebby exterior appearance
* Arachnoid granulation, small protrus ...
came to refer to a layer around the brain; the term ''retiform'' came to refer to the ''retina''.
Between 1011 and 1021 CE,
Ibn Al-Haytham
Ḥasan Ibn al-Haytham, Latinized as Alhazen (; full name ; ), was a medieval mathematician, astronomer, and physicist of the Islamic Golden Age from present-day Iraq.For the description of his main fields, see e.g. ("He is one of the pri ...
published numerous experiments demonstrating that sight occurs from light reflecting from objects into the eye. This is consistent with
intromission theory
Visual perception is the ability to interpret the surrounding environment through photopic vision (daytime vision), color vision, scotopic vision (night vision), and mesopic vision (twilight vision), using light in the visible spectrum reflec ...
and against
emission theory
Emission theory, also called emitter theory or ballistic theory of light, was a competing theory for the special theory of relativity, explaining the results of the Michelson–Morley experiment of 1887. Emission theories obey the principle of rel ...
, the theory that sight occurs from rays emitted by the eyes. However, Ibn Al-Haytham decided that the retina could not be responsible for the beginnings of vision because the image formed on it was inverted. Instead he decided it must begin at the surface of the lens.
In 1604,
Johannes Kepler worked out the optics of the eye and decided that the retina must be where sight begins. He left it up to other scientists to reconcile the inverted retinal image with our perception of the world as upright.
In 1894,
Santiago Ramón y Cajal
Santiago Ramón y Cajal (; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or Me ...
published the first major characterization of retinal neurons in ''Retina der Wirbelthiere'' (''The Retina of Vertebrates'').
George Wald,
Haldan Keffer Hartline
Haldan Keffer Hartline (December 22, 1903 – March 17, 1983) was an American physiologist who was a co-recipient (with George Wald and Ragnar Granit) of the 1967 Nobel Prize in Physiology or Medicine for his work in analyzing the neurophysiolog ...
, and
Ragnar Granit
Ragnar Arthur Granit (30 October 1900 – 12 March 1991) was a Finnish-Swedish scientist who was awarded the Nobel Prize in Physiology or Medicine in 1967 along with Haldan Keffer Hartline and George Wald "for their discoveries concerning the ...
won the 1967
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for their scientific research on the retina.
A recent
University of Pennsylvania
The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...
study calculated that the approximate
bandwidth
Bandwidth commonly refers to:
* Bandwidth (signal processing) or ''analog bandwidth'', ''frequency bandwidth'', or ''radio bandwidth'', a measure of the width of a frequency range
* Bandwidth (computing), the rate of data transfer, bit rate or thr ...
of human retinas is 8.75 megabits per second, whereas a
guinea pig
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
's retinal transfer rate is 875 kilobits per second.
MacLaren
Maclaren is a manufacturer of baby buggies, strollers and carriers based in Norwalk, Connecticut.
Product range
Strollers based around Owen Maclaren's original design are sold in over 50 countries under the Maclaren brand. These include the Ma ...
& Pearson and colleagues at
University College London
, mottoeng = Let all come who by merit deserve the most reward
, established =
, type = Public research university
, endowment = £143 million (2020)
, budget = ...
and
Moorfields Eye Hospital
Moorfields Eye Hospital is a specialist NHS eye hospital in Finsbury in the London Borough of Islington in London, England run by Moorfields Eye Hospital NHS Foundation Trust. Together with the UCL Institute of Ophthalmology, which is adjacen ...
in London, in 2006, showed that
photoreceptor cells
A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...
could be transplanted successfully in the mouse retina if donor cells were at a critical developmental stage. Recently Ader and colleagues in Dublin showed, using the electron microscope, that transplanted photoreceptors formed synaptic connections.
In 2012,
Sebastian Seung
Hyunjune Sebastian Seung (English: /sung/ or əŋ ) is President at Samsung Electronics & Head of Samsung Research and Anthony B. Evnin Professor in the Princeton Neuroscience Institute and Department of Computer Science. Seung has done influen ...
and his laboratory at
MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
launched
EyeWire, an online
Citizen science game where players trace neurons in the retina. The goals of the EyeWire project are to identify specific cell types within the known broad classes of retinal cells, and to
map the connections between neurons in the retina, which will help to determine how vision works.
Additional images
File:Three Main Layers of the Eye.png, The structures of the eye labeled
File:Three Internal chambers of the Eye.svg, Another view of the eye and the structures of the eye labeled
File:Retinal Image.png, Illustration of image as 'seen' by the retina independent of optic nerve and striate cortex processing.
See also
*
Adeno associated virus and gene therapy of the human retina
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
In 2008, three independent research groups reported that patients with the rare genetic retinal disease Leber's congenital amaurosis had be ...
*
Charles Schepens
Charles Louis Schepens (March 13, 1912 – March 28, 2006) was an influential Belgian (later American) ophthalmologist, regarded by many in the profession as "the father of modern retinal surgery",American Academy of Ophthalmology2003 Laureate A ...
– "the father of modern retinal surgery"
*
Evolution of the eye
Many scientists have found the evolution of the eye attractive to study because the eye distinctively exemplifies an convergent evolution, analogous organ (anatomy), organ found in many Taxon, animal forms. Simple light detection is found in bac ...
*
Duplex retina
A duplex retina is a retina consisting of both rod cells and cone cells, which are the photoreceptor cells for two parallel but mostly separate visual systems. The rods enable the scotopic visual system, which is active in dim light. The cones ...
*
Retinal scan
A retinal scan is a biometric technique that uses unique patterns on a person's retina blood vessels. It is not to be confused with other ocular-based technologies: iris recognition, commonly called an "iris scan", and eye vein verification that ...
*
Retinal vein occlusion
Central retinal vein occlusion, also CRVO, is when the central retinal vein becomes occluded, usually through thrombosis. The central retinal vein is the venous equivalent of the central retinal artery and both may become occluded. Since the centr ...
*
*
Rhodopsin
*
Persistence of vision
Persistence of vision traditionally refers to the optical illusion that occurs when visual perception of an object does not cease for some time after the rays of light proceeding from it have ceased to enter the eye.
The illusion has also been d ...
References
Further reading
*
S. Ramón y Cajal, ''Histologie du Système Nerveux de l'Homme et des Vertébrés'', Maloine, Paris, 1911.
*
*
*
*
*
External links
Histology of the Eye edited by William Krause, Dept. Pathology and Anatomical science, University of Missouri School of Medicine
* Kolb, H., Fernandez, E., & Nelson, R. (2003)
Webvision: The neural organization of the vertebrate retina Salt Lake City, Utah: John Moran Eye Center,
University of Utah
The University of Utah (U of U, UofU, or simply The U) is a public research university in Salt Lake City, Utah. It is the flagship institution of the Utah System of Higher Education. The university was established in 1850 as the University of De ...
. Retrieved 22 July 2014.
Demo: Artificial Retina MIT Technology Review, September 2004. Reports on implant research at
Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology, and editorially independent of the university. It was founded in 1899 as ''The Technology Review'', and was re-launched without "The" in ...
Successful photoreceptor transplantation MIT Technology Review, November 2006. How stem cells might restore sight
Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology, and editorially independent of the university. It was founded in 1899 as ''The Technology Review'', and was re-launched without "The" in ...
Australian Vision Prosthesis Group, Graduate School of Biomedical Engineering,
University of New South Wales
The University of New South Wales (UNSW), also known as UNSW Sydney, is a public research university based in Sydney, New South Wales, Australia. It is one of the founding members of Group of Eight, a coalition of Australian research-intensiv ...
RetinaCentral Genetics and Diseases of the Human Retina at
University of Würzburg
The Julius Maximilian University of Würzburg (also referred to as the University of Würzburg, in German ''Julius-Maximilians-Universität Würzburg'') is a public research university in Würzburg, Germany. The University of Würzburg is one of ...
Retinal layers image.NeuroScience 2nd Ed at
United States National Library of Medicine
The United States National Library of Medicine (NLM), operated by the United States federal government, is the world's largest medical library.
Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health. Its ...
Jeremy Nathans's Seminars: "The Vertebrate Retina: Structure, Function, and Evolution"Retina – Cell Centered Database*
*
{{Authority control
Visual system
Human eye anatomy