Melanopsin is a type of

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 p ...

belonging to a larger family of light-sensitive

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 retin ...

proteins called

opsin 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 pro ...

s and encoded by the gene ''Opn4''. In the mammalian

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 focused two-dimensional image of the visual world on the retina, which then ...

, there are two additional categories of opsins, both involved in the formation of visual images:

rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction ...

and

photopsin Vertebrate visual opsins are a subclass of ciliary opsins and mediate vision in vertebrates. They include the opsins in human rod and cone cells. They are often abbreviated to ''opsin'', as they were the first opsins discovered and are still th ...

(types I, II, and III) in the rod and

cone 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 con ...

photoreceptor cells, respectively. In humans, melanopsin is found in

intrinsically photosensitive retinal ganglion cells 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 ...

(ipRGCs). It is also found in the iris of mice and primates. Melanopsin is also found in rats,

amphioxus The lancelets ( or ), also known as amphioxi (singular: amphioxus ), consist of some 30 to 35 species of "fish-like" benthic filter feeding chordates in the order Amphioxiformes. They are the modern representatives of the subphylum Cephalochorda ...

, and other chordates. ipRGCs are photoreceptor cells which are particularly sensitive to the absorption of short-wavelength (blue) visible light and communicate information directly to the area of the brain called the

suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regula ...

(SCN), also known as the central "body clock", in mammals. Melanopsin plays an important non-image-forming role in the

setting Setting may refer to: * A location (geography) where something is set * Set construction in theatrical scenery * Setting (narrative), the place and time in a work of narrative, especially fiction * Setting up to fail a manipulative technique to eng ...

of circadian rhythms as well as other functions. Mutations in the ''Opn4'' gene can lead to clinical disorders, such as

Seasonal Affective Disorder Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. Common symptoms include sleeping too much, having li ...

(SAD). According to one study, melanopsin has been found in eighteen sites in the human brain (outside the retinohypothalamic tract), intracellularly, in a granular pattern, in the cerebral cortex, the cerebellar cortex and several phylogenetically old regions, primarily in neuronal soma, not in nuclei. Melanopsin is also expressed in human cones. However, only 0.11% to 0.55% of human cones express melanopsin and are exclusively found in the peripheral regions of the retina. The human peripheral retina senses light at high intensities that is best explained by four different photopigment classes.

Discovery

Melanopsin was discovered by

Ignacio Provencio Ignacio Provencio (born 29 June 1965) is an American neuroscientist and the discoverer of melanopsin, an opsin found in specialized photosensitive ganglion cells of the mammalian retina. Provencio served as the program committee chair of the Societ ...

as a new

in the

melanophore Chromatophores are cells that produce color, of which many types are pigment-containing cells, or groups of cells, found in a wide range of animals including amphibians, fish, reptiles, crustaceans and cephalopods. Mammals and birds, in cont ...

s, or light-sensitive skin cells, of the

African clawed frog The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws o ...

in 1998. A year later, researchers found that mice without any rods or

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 ...

, the cells involved in image-forming vision, still entrained to a light-dark cycle. This observation led to the conclusion that neither rods nor cones, located in the outer

, are necessary for circadian entrainment and that a third class of photoreceptor exists in the mammalian eye. Provencio and colleagues then found in 2000 that melanopsin is also present in mouse retina, specifically in

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 ...

, and that it mediates non-visual photoreceptive tasks. Melanopsin is encoded by the ''Opn4'' gene with

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

s in a variety of organisms. These retinal ganglion cells were found to be innately photosensitive, since they responded to light even while isolated, and were thus named intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). They constitute a third class of

photoreceptor cell 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 ...

s in the mammalian retina, besides the already known rods and cones, and were shown to be the principal conduit for light input to circadian photoentrainment. In fact, it was later demonstrated by Satchidananda Panda and colleagues that melanopsin pigment may be involved in entrainment of a

circadian oscillator A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time. Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's current solar day ...

to light cycles in mammals since melanopsin was necessary for blind mice to respond to light.

Species distribution

Mammals have

orthologous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

melanopsin genes named ''Opn4m'', which are derived from one branch of the ''Opn4'' family, and are approximately 50-55% conserved. However, non-mammalian vertebrates, including chickens and zebrafish, have another version of the melanopsin gene, ''Opn4x'', which appears to have a distinct lineage that diverged from ''Opn4m ''about 360 million years ago. Mammals lost the gene ''Opn4x'' relatively early in their evolution, leading to a general reduction in photosensory capability. It is thought that this event can be explained by the fact that this occurred during the time in which nocturnal mammals were evolving.

Structure

The human melanopsin gene, ''opn4'', is expressed in

ipRGCs 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 ...

, which comprises only 1-2% of RGCs in the inner mammalian retina, as studied by

Samer Hattar Samer Hattar ( ar, سامر حتر) is a chronobiologist and a leader in the field of non-image forming photoreception. He is the Chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health, part of the National ...

and colleagues. The gene spans approximately 11.8 kb and is mapped to the long arm of

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

. The gene includes nine

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

s and ten

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

compared to the four to seven exons typically found in other human opsins. In non-mammalian vertebrates, melanopsin is found in a wider subset of retinal cells, as well as in photosensitive structures outside the retina, such as the

iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants * Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional ent ...

muscle of the eye, deep brain regions, the

pineal gland The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep, sleep patterns in both circadian rhythm, circ ...

, and the skin.

Paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

of ''Opn4'' include

OPN1LW OPN1LW is a gene on the X chromosome that encodes for long wave sensitive (LWS) opsin, or red cone photopigment. It is responsible for perception of visible light in the yellow-green range on the visible spectrum (around 500-570nm). The gene con ...

OPN1MW Green-sensitive opsin is a protein that in humans is encoded by the ''OPN1MW'' gene. OPN1MW2 OPN1MW2 is a duplication of the OPN1MW gene, which encodes the medium wavelength sensitive (MWS) photopsin. The gene duplication is present in about 50% ...

and encephalopsin. Melanopsin, like all other animal

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 ...

(e.g.

), is a G-protein-coupled receptor (GPCR). The melanopsin protein has an extarcellular

N-terminal domain The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

, an intracellular

C-terminal domain The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

, and seven

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

spanning through the plasma membrane. The seventh helix has a

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

that corresponds to Lys296^7.43 in

cattle Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...

and that is conserved in almost all opsins. This lysine binds covalently

via a

Schiff-base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...

, which makes melanopsin light sensitive. In fact this is abolished if the lysine is replaced by an

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...

. Melanopsin is more closely related to

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

visual opsins, which are rhabdomeric opsin, than to

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, ...

visual opsins, which are cliary opsins. This is also reflected by the downstream

signaling cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...

, melanopsin couples in ipRGCs to the

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 G(q), G(11), and G(14), which are all of the G(q)-type. In fact, they can functionally replace each other, as a knocking out only two of them has no

phenotypical In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

effect. The G-proteins activate the

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

PLCB4, which causes the TRP-channels

TRPC6 Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily. It has been associated ...

and

TRPC7 Transient receptor potential cation channel, subfamily C, member 7, also known as TRPC7, is a human gene encoding a protein of the same name. See also * TRPC TRPC is a family of transient receptor potential cation channels in animals. TRPC ch ...

mediate to open so that the cell depolarizes. This is like in the photoreceptor cells of the

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 species ...

eye, and in contrast to the vertebrate rod and

cells, where

phototransduction Visual phototransduction is the transduction (physiology), sensory transduction process of the visual system by which light is detected to yield Action potential, nerve impulses in the rod cells and cone cells in the retina of the eye in humans and ...

eventually makes the cells hyperpolarize. Like other rhabdomeric opsins, Melanopsin has intrinsic photoisomerase activity.

Function

Melanopsin-containing ganglion cells, like rods and cones, exhibit both light and dark

adaptation In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the po ...

; they adjust their sensitivity according to the recent history of light exposure. However, while rods and cones are responsible for the reception of images, patterns, motion, and color, melanopsin-containing

contribute to various reflexive responses of the brain and body to the presence of light. Evidence for melanopsin's physiological light detection has been tested in mice. A mouse cell line that is not normally photosensitive, Neuro-2a, is rendered light-sensitive by the addition of human melanopsin. The photoresponse is selectively sensitive to short-wavelength light (peak absorption ~479 nm), and has an intrinsic photoisomerase regeneration function that is chromatically shifted to longer wavelengths. Melanopsin photoreceptors are sensitive to a range of wavelengths and reach peak light absorption at blue light wavelengths around 480 nanometers. Other wavelengths of light activate the melanopsin signaling system with decreasing efficiency as they move away from the optimum 480 nm. For example, shorter wavelengths around 445 nm (closer to violet in the

visible spectrum The visible spectrum is the portion of the electromagnetic spectrum that is visual perception, visible to the human eye. Electromagnetic radiation in this range of wavelengths is called ''visible light'' or simply light. A typical human eye wil ...

) are half as effective for melanopsin photoreceptor stimulation as light at 480 nm. Melanopsin in the iris of some, primarily nocturnal, mammals closes the iris when it is exposed to light. This local pupil light reflex (PLR) is absent from primates, even though their irises express melanopsin.

Mechanism

When light with an appropriate frequency enters the eye, it activates the melanopsin contained in

(ipRGCs), triggering an

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, ...

. These neuronal electrical signals travel through neuronal

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 po ...

s to specific brain targets, such as the center of pupillary control called the

olivary pretectal nucleus In neuroanatomy, the pretectal area, or pretectum, is a midbrain structure composed of seven nuclei and comprises part of the subcortical visual system. Through reciprocal bilateral projections from the retina, it is involved primarily in mediati ...

(OPN) of the midbrain. Consequently, stimulation of melanopsin in ipRGCs mediates behavioral and physiological responses to light, such as pupil constriction and inhibition of melatonin release from the

. The ipRGCs in the mammalian retina are one terminus of the

retinohypothalamic tract In neuroanatomy, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), whi ...

that projects to the

(SCN) of the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

. The suprachiasmatic nucleus is sometimes described as the brain's "master clock", as it maintains the

circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogeno ...

, and nerve signals from ipRGCs to the SCN entrain the internal circadian rhythm to the rising and setting of the sun. The SCN also receives input from rods and cones through the retinohypothalamic tract, so information from all three photosensitive cell types (rods, cones, and ipRGCs) in the mammalian retina are transmitted to the (SCN) SCN. Melanopsin-containing ganglion cells are thought to influence these targets by releasing the

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

and pituitary adenylate cyclase activating polypeptide (PACAP) from their axon terminals. Melanopsin-containing ganglion cells also receive input from rods and cones that can add to the input to these pathways.

Effects on circadian rhythm

Melanopsin serves an important role in the photoentrainment of circadian rhythms in mammals. An organism that is photoentrained has aligned its activity to an approximately 24-hour cycle, the

solar cycle The solar cycle, also known as the solar magnetic activity cycle, sunspot cycle, or Schwabe cycle, is a nearly periodic 11-year change in the Sun's activity measured in terms of variations in the number of observed sunspots on the Sun's surfa ...

on Earth. In mammals, melanopsin expressing axons target the suprachiasmatic nucleus (SCN) through the

(RHT). In mammals, the eye is the main photosensitive organ for the transmission of light signals to the brain. However, blind humans are still able to entrain to the environmental light-dark cycle, despite having no conscious perception of the light. One study exposed subjects to bright light for a prolonged duration of time and measured their melatonin concentrations. Melatonin was not only suppressed in visually unimpaired humans, but also in blind participants, suggesting that the photic pathway used by the circadian system is functionally intact despite blindness. Therefore, physicians no longer practice enucleation of blind patients, or removal of the eyes at birth, since the eyes play a critical role in the photoentrainment of the circadian pacemaker. In mutant breeds of mice that lacked only rods, only cones, or both rods and cones, all breeds of mice still entrained to changing light stimuli in the environment, but with a limited response, suggesting that rods and

are not necessary for circadian photoentrainment and that the mammalian eye must have another photopigment required for the regulation of the circadian clock. Melanopsin- knockout mice display reduced photoentrainment. In comparison to wild-type mice that expressed melanopsin normally, deficits in light-induced phase shifts in locomotion activity were noted in melanopsin-null mice (''Opn4 -/-''). These melanopsin-deficient mice did not completely lose their circadian rhythms, as they were still able to entrain to changing environmental stimuli, albeit more slowly than normal. This indicated that, although melanopsin is sufficient for entrainment, it must work in conjunction with other photopigments for normal photoentrainment activity. Triple-mutant mice that were rod-less, cone-less, and melanopsin-less display a complete loss in the circadian rhythms, so all three photopigments in these photoreceptors,

and melanopsin, are necessary for photoentrainment. Therefore, there is a functional redundancy between the three photopigments in the photoentrainment pathway of mammals. Deletion of only one photopigment does not eliminate the organism's ability to entrain to environmental light-dark cycles, but it does reduce the intensity of the response.

Regulation

Melanopsin undergoes

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

on its intracellular carboxy tail as a way to deactivate its function. Compared to other opsins, melanopsin has an unusually long carboxy tail that contains 37

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

and

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

amino acid sites that could undergo phosphorylation. However, a cluster of seven amino acids are sufficient to deactivate zebrafish melanopsin. These sites are dephosphorylated when melanopsin is exposed to light and are unique from those that regulate rhodopsin. They are important for proper response to calcium ions in ipRGCs; lack of functional phosphorylation sites, particularly at serine-381 and serine-398, reduce the cell's response to light-induced calcium ion influx when voltage-gated calcium ion channels open. In terms of the gene Opn4,

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

(DA) is a factor in the regulation of melanopsin

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

in ipRGCs.

Clinical significance

The discovery of the role of melanopsin in non-image forming vision has led to a growth in

optogenetics Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individ ...

. This field has shown promise in clinical applications, including the treatment of human eye diseases such as

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 ...

and

diabetes 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 ap ...

. A

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

in Opn4, P10L, has been implicated in 5% of patients with

(SAD). This is a condition in which people experience depressive thoughts in the winter due to decreased available light. Additionally, a melanopsin based receptor has been linked to

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

pain.

Restoration of vision

There has been recent research on the role of melanopsin in

optogenetic Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individ ...

therapy for patients with the degenerative eye disease

(RP). Reintroducing functional melanopsin into the eyes of mice with retinal degeneration restores the pupillary light reflex (PLR). These same mice could also distinguish light stimuli from dark stimuli and showed increased sensitivity to room light. The higher sensitivity demonstrated by these mice shows promise for vision restoration that may be applicable to humans and human eye diseases.

Control of sleep/wake patterns

Melanopsin may aid in controlling sleep cycles and wakefulness. Tsunematsu and colleagues created

transgenic 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 the ...

mice that expressed melanopsin in

hypothalamic The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...

orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy) ...

neurons. With a short 4-second pulse of blue light (guided by optical fibers), the transgenic mice could successfully transition from slow-wave sleep (SWS), which is commonly known as "deep sleep," to long-lasting wakefulness. After switching off the blue light, the hypothalamic

neurons showed activity for several tens of seconds. It has been shown that rods and cones play no role in the onset of sleep by light, distinguishing them from ipRGCs and melanopsin. This provides strong evidence that there is a link between ipRGCs in humans and alertness, particularly with high frequency light (e.g. blue light). Therefore, melanopsin can be used as a therapeutic target for controlling the sleep-wake cycle.

Regulation of blood glucose levels

In a paper published by Ye and colleagues in 2011, melanopsin was utilized to create an optogenetic synthetic transcription device that was tested in a therapeutic setting to produce Fc-glucagon-like peptide 1 (Fc-GLP-1), a fusion protein that helps control blood glucose levels in mammals with Type II diabetes, Type II Diabetes. The researchers subcutaneously implanted mice with microencapsulated transgenic HEK 293 cells that were cotransfected with two vectors including the melanopsin gene and the gene of interest under an NFAT (Nuclear factor of activated T-cells, nuclear factor of activated T cells) promoter, respectively. It is through this engineered pathway that they successfully controlled the expression of Fc-GLP-1 in doubly recessive diabetic mice and reduced hyperglycemia, or high blood glucose levels, in these mice. This shows promise for the use of melanopsin as an optogenetic tool for the treatment of Type II diabetes.