HOME

TheInfoList



OR:

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 (chemistry), moiety of photosensitive chromoproteins, such as the pigments involved in ph ...
belonging to a larger family of light-sensitive retinal 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 (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...
, 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 a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
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 t ...
(types I, II, and III) in the rod and
cone In geometry, a cone is a three-dimensional figure that tapers smoothly from a flat base (typically a circle) to a point not contained in the base, called the '' apex'' or '' vertex''. A cone is formed by a set of line segments, half-lines ...
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 ( ), also known as amphioxi (: amphioxus ), consist of 32 described species of somewhat fish-like benthic filter feeding chordates in the subphylum Cephalochordata, class Leptocardii, and family Branchiostomatidae. Lancelets div ...
, 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 small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive r ...
(SCN), also known as the central "body clock", in mammals. Melanopsin plays an important non-image-forming role in the setting 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 typically have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. It is commonly, but not always, associated w ...
(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 as a new
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 ...
in the melanophores, or light-sensitive skin cells, of the
African clawed frog The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African Aquatic animal, aquatic frog of the family Pipidae. Its name is derived from the ...
in 1998. A year later, researchers found that mice without any rods or
cones In geometry, a cone is a three-dimensional figure that tapers smoothly from a flat base (typically a circle) to a point not contained in the base, called the ''apex'' or '' vertex''. A cone is formed by a set of line segments, half-lines, ...
, 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
retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...
, 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, 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 speci ...
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 radiation ...
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 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 speci ...
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, which comprises only 1-2% of RGCs in the inner mammalian retina, as studied by Samer Hattar and colleagues. The gene spans approximately 11.8 kb and is mapped to the long arm of chromosome 10. 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., gen ...
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 i ...
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 muscle of the eye, deep brain regions, the
pineal gland The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...
, and the skin. Paralogs of ''Opn4'' include
OPN1LW OPN1LW is a gene on the X chromosome that encodes for long wave sensitive (LWS) opsin, or red cone photopigment. The OPN1LW gene provides instructions for making an opsin pigment that is more sensitive to light in the yellow/orange part of the vis ...
,
OPN1MW Green-sensitive opsin is a protein that in humans is encoded by the ''OPN1MW'' gene. OPN1MW2 is a similar opsin. The OPN1MW gene provides instructions for making an opsin pigment that is more sensitive to light in the middle of the visible spect ...
,
rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
and encephalopsin. Melanopsin, like all other animal opsins (e.g.
rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
), 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 amin ...
, an intracellular
C-terminal domain The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy 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 t ...
, and seven
alpha helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
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. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
that corresponds to Lys2967.43 in
cattle Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
and that is conserved in almost all opsins. This lysine binds covalently
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 ret ...
via a Schiff-base, 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 sid ...
. Melanopsin is more closely related to
invertebrate Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordata, chordate s ...
visual opsins, which are rhabdomeric opsin, than to
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
visual opsins, which are cliary opsins. This is also reflected by the downstream signaling cascade, 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 ...
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 phenotypic trait, traits of an organism. The term covers the organism's morphology (biology), morphology (physical form and structure), its Developmental biology, develo ...
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 i ...
PLCB4, which causes the TRP-channels
TRPC6 Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a protein encoded in the human by the ''TRPC6'' gene. TRPC6 is a transient receptor potential channel of the c ...
and TRPC7 mediate to open so that the cell depolarizes. This is like in the photoreceptor cells of the
Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
eye, and in contrast to the vertebrate rod and
cone In geometry, a cone is a three-dimensional figure that tapers smoothly from a flat base (typically a circle) to a point not contained in the base, called the '' apex'' or '' vertex''. A cone is formed by a set of line segments, half-lines ...
cells, where phototransduction 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 p ...
; 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 ipRGCs 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 spectral band, band 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). The optica ...
) 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
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), triggering an
action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...
. These neuronal electrical signals travel through neuronal
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
s to specific brain targets, such as the center of pupillary control called the olivary pretectal nucleus (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 Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...
release from the
pineal gland The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...
. 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), ...
that projects to the
suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive r ...
(SCN) of the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. 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 oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the env ...
, 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, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
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 periodic 11-year change in the Sun's activity measured in terms of Modern Maximum, variations in the number of observed sunspots on the Sun ...
on Earth. In mammals, melanopsin expressing axons target the suprachiasmatic nucleus (SCN) through 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), ...
(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 Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...
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
cones In geometry, a cone is a three-dimensional figure that tapers smoothly from a flat base (typically a circle) to a point not contained in the base, called the ''apex'' or '' vertex''. A cone is formed by a set of line segments, half-lines, ...
are not necessary for circadian photoentrainment and that the mammalian eye must have another photopigment required for the regulation of the
circadian A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment (is entrai ...
clock. Melanopsin-
knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
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,
rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
,
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 t ...
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 biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
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 − ...
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 when dissolved in water), 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 chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
(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 Gene expression, expression of Channelrhodopsin, light-sensitive ion channels, Halorhodopsin, pumps or Photoactivated ade ...
. This field has shown promise in clinical applications, including the treatment of human eye diseases such as
retinitis pigmentosa Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visua ...
and
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
. 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. Missense mutations change amino acids, which in turn alt ...
in Opn4, P10L, has been implicated in 5% of patients with
Seasonal Affective Disorder Seasonal affective disorder (SAD) is a mood disorder subset in which people who typically have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. It is commonly, but not always, associated w ...
(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 complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...
pain.


Restoration of vision

There has been recent research on the role of melanopsin in optogenetic therapy for patients with the degenerative eye disease
retinitis pigmentosa Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visua ...
(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
orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief loss ...
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
orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief loss ...
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 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...
. The researchers subcutaneously implanted mice with microencapsulated transgenic
HEK 293 cells Human embryonic kidney 293 cells, also often referred to as HEK 293, HEK-293, 293 cells, are an immortalised cell line derived from HEK cells isolated from a female fetus in the 1970s. The HEK 293 cell line has been widely used in research for de ...
that were cotransfected with two vectors including the melanopsin gene and the gene of interest under an NFAT ( 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 Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...
, 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.


See also

* Light effects on circadian rhythm * Opsins * Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) * Suprachiasmatic nucleus (SCN) *
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), ...


References


Further reading

* {{G protein-coupled receptors G protein-coupled receptors Circadian rhythm Human proteins