Meeting Abstract
Mammals have three major classes of photoreceptor cells in the retina, rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Both rod and cone photoreceptors are located in the outer retina and transduce light-activated signals through the retina to retinal ganglion cells (RGCs). ipRGCs are a heterogeneous subset of RGCs that form the principal conduit for retinal input to brain regions that control non-image forming functions, such as pupillary light reflex and circadian photoentrainment. Under bright light conditions ipRGCs are directly activated by their invertebrate-like photopigment, melanopsin. In dim light which is unable to activate melanopsin, ipRGCs receive input from rod and cone pathways. RdgB2 is a mammalian homolog of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction and is expressed in the retinal ganglion cell layer of the retina. The expression pattern of RdgB2 suggests that it might function in the melanopsin-dependent activation of ipRGCs. Surprisingly, RdgB2-/- mice have normal pupillary light reflex and circadian photoentrainment in bright light, but show a defect in both behaviors in dim light. We have found that the RdgB2 protein was not expressed in ipRGCs, but instead in a subset of GABAergic amacrine cells. RdgB2-positive amacrine cells provide inhibitory feedback onto bipolar cells, which is essential for maintaining bipolar cell response amplitude. We have provided the first evidence of RdgB2 function in the mammalian retina and have shown that it is required to transduce rod-driven input to ipRGCs for activation in dim light.
