An invertebrate‐like phototransduction cascade mediates light detection in the chicken retinal ganglion cells

Abstract

Prebilaterian animals perceived ambient light through nonvisual rhabdomeric photoreceptors (RPs), which evolved as support of the chordate visual system. In vertebrates, the identity of nonvisual photoreceptors and the phototransduction cascade involved in nonimage forming tasks remain uncertain. We investigated whether chicken retinal ganglion cells (RGCs) could be nonvisual photoreceptors and the nature of the photocascade involved. We found that primary cultures of chicken embryonic RGCs express such RP markers as transcription factors Pax6 and Brn3, photopigment melanopsin, and G-protein q but not markers for ciliary photoreceptors (alpha-transducin and Crx). To investigate the photoreceptive capability of RGCs, we assessed the direct effect of light on 3H-melatonin synthesis in RGC cultures synchronized to 12:12 h light-dark cycles. In constant dark, RGCs displayed a daily variation in 3H-melatonin levels peaking at subjective day, which was significantly inhibited by light. This light effect was further increased by the chromophore all-trans-retinal and suppressed by specific inhibitors of the invertebrate photocascade involving phosphoinositide hydrolysis (100 microM neomycin; 5 microM U73122) and Ca2+ mobilization (10 mM BAPTA; 1 mM lanthanum). The results demonstrate that chicken RGCs are intrinsically photosensitive RPs operating via an invertebrate-like phototransduction cascade, which may be responsible for early detection of light before vision occurs.

Horizontal cells expressing melanopsin x are novel photoreceptors in the avian inner retina

“…Conversely, when the light is on, cones and rods become hyperpolarized, stopping the release of glutamate and thus preventing the depolarization and subsequent HC response. In addition to their typical role in the retinal circuits, in nonmammalian vertebrates HCs may conserve vestiges of ancient photoreceptor cells (Scheme 1, scenario 2) as clearly demonstrated for ipRGCs (2,6,17,18). In teleosts, it has been reported that retinal HCs expressing VA opsin or OPN4 can intrinsically respond to light (28,29).…”

“…In teleosts, it has been reported that retinal HCs expressing VA opsin or OPN4 can intrinsically respond to light (28,29). OPN4 is found in brain, iris, and retinal cells of vertebrates (1,3,5,6,12,(17)(18)(19) and highly conserved through evolution (38). In mammals OPN4 is confined to ipRGCs; however, the distribution of multiple Opn4s (Opn4m and Opn4x) in diverse retinal cell types of nonmammalian vertebrates suggests a biological function of higher complexity (see review in ref.…”

“…5 C and G). On the contrary, when specific inhibitors of the visual phototransduction cascade were used, such as the pertussis toxin (500 nM) that disrupts signaling through the Gi/o protein α-transducin or zaprinast (0.1 M), a specific phosphodiesterase 6 (PDE6) inhibitor (6,17), light responses were not affected in the cultures (Fig. S5 D and E).…”

“…Evidence suggests that during the course of evolution, mammals lost some visual opsins and Opn4x as they entered the nocturnal niche. In the chicken retina, different laboratories have reported the expression of Opn4 genes in outer nuclear, inner nuclear, and ganglion cell layer (GCL) cells (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). At the protein level, OPN4M was shown to be restricted to ipRGCs, whereas OPN4X was found in the GCL at embryo day 8 (E8) but mostly in PROX1 (+) horizontal cells (HCs) by E15 (21); the homeobox gene PROX1 is a universal HC marker that is expressed from E8 forward (22,23).…”

Phototransduction in ganglion-cell photoreceptors

“…Another indirect line of evidence comes from studies of chick RGCs, a small percentage of which express melanopsin [7]. In relatively pure cultures of embryonic chick ganglion cells, transcripts for G q but not transducin have been identified [8]. In the same cultures, light suppresses the release of melatonin and this effect, which may be mediated by melanopsin, requires PLC.…”