Photoreceptor signaling in primate retina

Project Summary/Abstract Human daylight vision is dominated by signaling in the fovea, a specialization unique to diurnal primates which is responsible for half of the retinal output and hence input to the higher visual centers. Our high-definition central vision is initiated in the cone photoreceptors which are packed in a dense and exquisite pixel array in the fovea. This unique arrangement together with the specialized retinal circuitry is key for the highest spatial and chromatic resolution attributed to our central vision. It is well known that the density and morphology of cone photoreceptors differ remarkably between foveal and peripheral primate retina, but our knowledge about the physiological and functional differences remain quite poor. Interestingly, our recent observations in primate retina have revealed that the time course of cone signals in the fovea is two-fold slower than in the peripheral retina consistent with the two-fold difference in the temporal sensitivity of our cone-mediated vision to high-frequency flicker. The broad goal of our project is to determine the full breadth of heterogeneities in cone signaling, “retinotopy of function”, across a range of visual inputs and functional properties. We will focus on three salient questions across three aims: 1) What are the differences in key functional properties of signals originating in the primate cone photoreceptors across the visual field? (2) Is cellular noise generated in cone phototransduction homogenous in cones across the visual field and what limits does it pose for cone function and perception? (3) Do foveal cones exhibit differences in function during natural vision compared to cones in rest of the primate retina? We will answer these questions using electrophysiological recordings of responses from cones in primate retina and models that describe cone function. The proposed work will provide a detailed insight into primate cone signaling especially in the fovea. Death of cone photoreceptors is the primary cause for vision loss in retinal diseases that attack the fovea such as macular degeneration. A therapy option that holds promise for such degenerative diseases is stem cell derived photoreceptor replacement therapy. Our study will provide the much-needed baseline information about foveal cone signaling to evaluate cone function in human stem cell derived retina for designing effective stem cell-based therapies as a way to ultimately cure degenerative retinal diseases such as macular degeneration and others.