Melanopsin signalling in mammalian iris and retina

Abstract

Lower vertebrates have an intrinsically-photosensitive iris and thus a local pupillary light reflex (PLR). In contrast, it has been a dogma that the PLR in mammals generally requires neuronal circuitry connecting the eye and the brain. We report here that an intrinsic component of the PLR is actually widespread in nocturnal and crepuscular mammals. In mouse, this intrinsic PLR requires the visual pigment, melanopsin. It also requires PLCβ4, the vertebrate homolog of the Drosophila NorpA phospholipase C mediating rhabdomeric phototransduction. The Plcβ4−/− genotype, besides removing the intrinsic PLR, also essentially eliminates the intrinsic light response of the M1-subtype of melanopsin-expressing, intrinsically-photosensitive retinal ganglion cells (M1-ipRGCs), by far the most photosensitive ipRGCs and with the largest responses. Ablating in mouse the expression of both TRPC6 and TRPC7, members of the TRP channel superfamily, likewise essentially eliminated the M1-ipRGC light response, but spared the intrinsic PLR. Thus, melanopsin signaling exists in both iris and retina, involving a PLCβ4-mediated pathway that nonetheless diverges in the two locations.

Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

“…The stimulation of melanopsin leads to the activation of a membrane bound signalling cascade involving Gq/11 type G-proteins, activation of PLCβ4 and ultimately the opening of downstream TRP type ion channels, TRPC6 and TRPC7. 49,[68][69][70][71][72][73] However, this model describes only the basic core components of what is likely to be a far more complicated signalling pathway and fails to account for the multiple types of photoresponse observed from individual pRGCs. It is currently unclear to what extent the precise mechanisms of melanopsin phototransduction are conserved between different pRGC subtypes, with the majority of detailed analysis performed to date conducted on M1-type pRGCs.…”

UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

“…Light is detected in the retina by opsin GPCRs and TRP channels can be activated downstream: TRPs contribute to melanopsin-activated phototransduction in intrinsically photosensitive retinal ganglion cells (8,9,11), and also mediate the light-sensitive ionic conductance in Drosophila phototransduction (3-5). As UVR activates TRPA1 in a retinal-dependent manner and retinal is the chromophore required for opsin activation, we investigated if UVR activates TRPA1 downstream of an opsin-mediated G protein signaling cascade by blocking G protein activation with either guanosine 5′-O-2-thiodiphosphate (GDPβS) or suramin (39)(40)(41).…”

“…More recently, members of the TRP family have been implicated in a wide range of sensory functions, including photosensation, chemosensation, thermosensation, and nociception (6,7). In mammalian phototransduction, TRPC channels mediate a light-sensitive current in intrinsically photoreceptive retinal ganglion cells, which are responsible for nonimage-forming visual processes in the human retina (8)(9)(10)(11). TRP channels are also expressed in the epidermis and are activated by noxious compounds, acidic pH, and temperature (12)(13)(14).…”

Calcium activates the light-dependent conductance in melanopsin-expressing photoreceptors of amphioxus

“…The amphioxus photocurrent is seemingly mediated by TRPclass channels (20), like in PLC-using visual receptors of invertebrates (9), and in ipRGCs (10)(11)(12)(13). Interestingly, TRP channels gated by intracellular Ca have been described in various systems (46)(47)(48).…”

“…Some reports argue against both calcium and DAG as critical signaling elements, hinting instead at a potential role for PIP 2 in channel gating (8), but firm evidence has yet to be garnered. As for the nature of the light-sensitive conductance, ion channels of the TRP superfamily have been implicated (10)(11)(12)(13).…”