Melanopsin

Melanopsin is a photopigment found in specialized photosensitive ganglion cells of the retina that are involved in the regulation of circadian rhythms and pupillary reflex. In structure, melanopsin is an opsin, a retinylidene protein variety of G-protein-coupled receptor. It is presumed that melanopsin signals through a G-protein of the Gq family, as invertebrate opsins are known to do, but this is not firmly established. It is also believed to be similar to invertebrate opsins in possessing an intrinsic photoisomerase activity.

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Discovery and function

Melanopsin was originally discovered in 1998 in specialized light-sensitive cells of frog skin by Dr. Ignacio Provencio and his colleagues.^[1] In 2000, Provencio showed that mammals, including humans, also produce melanopsin and that it is found only in a rare subtype of retinal ganglion cells, the output cells of the retina.

The first recordings of light responses from melanopsin ganglion cells were obtained by Dr. David Berson and colleagues at Brown University.^[2]

They also showed that these responses persisted when pharmacological agents blocked synaptic communication in the retina, and when single melanopsin ganglion cells were physically isolated from other retinal cells. These findings showed that melanopsin ganglion cells are intrinsically photosensitive, and thus constitute a third class of photoreceptors in the mammalian retina, joining the better known rod and cone photoreceptors.^[3]

Further studies from his lab have concluded that melanopsin ganglion cells exhibit both light and dark adaptation, that is, that they adjust their sensitivity according to the recent history of light exposure.^[4] In this respect, they are similar to rods and cones. However, whereas rods and cones are responsible for the analysis of images, patterns, motion and color, melanopsin ganglion cells are responsible for various reflexive responses of the brain and body to the presence of daylight.

Mechanism

When light activates the melanopsin signaling system, the melanopsin-containing ganglion cells discharge nerve impulses, which are conducted through their axons in the optic nerve to specific brain targets.

These targets include the suprachiasmatic nucleus of the hypothalamus (the master pacemaker of circadian rhythms) and the olivary pretectal nucleus (a center responsible for controlling the pupil of the eye).

Melanopsin ganglion cells are thought to influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP).

Effects on light entrainment

Experiments have shown that light entrainment, by which periods of behavioral activity or inactivity (sleep) are synchronized with the light-dark cycle, is not as effective in melanopsin knockout mice.

By contrast, mice lacking rods and cones still exhibit circadian entrainment and pupillary reflex.

Distribution in different species

Melanopsin has a very similar pattern of tissue distribution among all mammals studied so far, including rodents, monkeys, and humans. Specifically, melanopsin is expressed only in the retina, and only in 1-2% of the ganglion cells.

In non-mammalian vertebrates, however, such as birds, fish and amphibians, melanopsin is found in certain other retinal cells, and also outside the retina in structures known or presumed to be directly photosensitive, such as the iris muscle of the eye, deep brain regions, the pineal gland, and the skin.

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