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 of ipRGCs were first noted in 1923 when rodless, coneless mice still responded to a light stimulus through pupil constriction, suggesting that rods and cones are not the only light sensitive neurons in the retina. It wasn't until the 1980s that advancements in research on these cells began. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light sensitive protein. Therefore they constitute a third class of photoreceptors, in addition to rod and cone 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 of ipRGCs were first noted in 1923 when rodless, coneless mice still responded to a light stimulus through pupil constriction, suggesting that rods and cones are not the only light sensitive neurons in the retina. It wasn't until the 1980s that advancements in research on these cells began. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light sensitive protein. Therefore they constitute a third class of photoreceptors, in addition to rod and cone cells. Compared to the rods and cones, the ipRGCs respond more sluggishly and signal the presence of light over the long term. They represent a very small subset (~1%) of the retinal ganglion cells. Their functional roles are non-image-forming and fundamentally different from those of pattern vision; they provide a stable representation of ambient light intensity. They have at least three primary functions. Photoreceptive ganglion cells have been isolated in humans where, in addition to regulating the circadian rhythm, they have been shown to mediate a degree of light recognition in rodless, coneless subjects suffering with disorders of rod and cone photoreceptors. Work by Farhan H. Zaidi and colleagues showed that photoreceptive ganglion cells may have some visual function in humans. The photopigment of photoreceptive ganglion cells, melanopsin, is excited by light mainly in the blue portion of the visible spectrum (absorption peaks at ~480 nanometers). The phototransduction mechanism in these cells is not fully understood, but seems likely to resemble that in invertebrate rhabdomeric photoreceptors. In addition to responding directly to light, these cells may receive excitatory and inhibitory influences from rods and cones by way of synaptic connections in the retina. The axons from these ganglia innervate regions of the brain related to object recognition, including the superior colliculus and dorsal lateral geniculate nucleus. These photoreceptor cells project both throughout the retina and into the brain. They contain the photopigment melanopsin in varying quantities along the cell membrane, including on the axons up to the optic disc, the soma, and dendrites of the cell. ipRGCs contain membrane receptors for the neurotransmitters glutamate, glycine, and GABA. Photosensitive ganglion cells respond to light by depolarizing thus increasing the rate at which they fire nerve impulses, which is opposite to that of other photoreceptor cells which hyperpolarize in response to light. Results of studies in mice suggest that the axons of ipRGCs are unmyelinated. Unlike other photoreceptor pigments, melanopsin has the ability to act as both the excitable photopigment and as a photoisomerase. Instead of requiring additional cells to revert between the two isoforms, from all-trans-retinal back into 11-cis-retinal before it can undergo another phototransduction, like the photoreceptor cones which rely on müller cells and retinal pigment epithelium cells for this conversion, melanopsin is able to isomerize all-trans-retinal into 11-cis-retinal when stimulated with light without help from additional cells. The two isoforms of melanopsin differ in their spectral sensitivity, for the 11-cis-retinal isoform is more responsive to shorter wavelengths of light, while the all-trans isoform is more responsive to longer wavelengths of light. ipRGCs are both pre- and postsynaptic to dopaminergic amacrine cells (DA cells) via reciprocal synapses, with ipRGCs sending excitatory signals to the DA cells and the DA cells sending inhibitory signals to the ipRGCs. These inhibitory signals are mediated through GABA which is co-released from the DA cells along with dopamine. Dopamine has functions in the light adaptation process by up-regulating melanopsin transcription in ipRGCs and thus increasing the photoreceptor's sensitivity. In parallel with the DA amacrine cell inhibition, somatostatin-releasing amacrine cells, themselves inhibited by DA amacrine cells, inhibit ipRGCs. Other synaptic inputs to ipRGC dendrites include cone bipolar cells and rod bipolar cells.