Most conscious vision in humans relies upon the fovea, a retinal structure that encodes the image in exceptional detail. Our goal is to understand the first steps of signal encoding in the fovea, which take place within its unusual population of photoreceptors. These foveal cones are morphologically distinct from their counterparts in the peripheral retina. Foveal cones have a tiny cross-section and dense packing, which allows them to form a uniquely fine pixel array. They also extend long axons to their postsynaptic cells. This allows the retinal circuitry to be displaced laterally from the light path of foveal cones, which sharpens the visual image. Our hypothesis is that, in addition to these anatomical features, foveal cones have physiological specializations that support the resolution of image detail. There is cause to think that their physiology does indeed differ from that of peripheral cones. For example, their unusual shape may influence the biochemical reactions of phototransduction as well as the nature of signal propagation from the site of phototransduction to the synaptic terminal. We propose to define the biophysical mechanisms of phototransduction in foveal cones (Aim 1) and to determine how the passive and active membrane properties of these cells further shape the light response as it spreads down the axon (Aim 2). Our approach centers on in vitro patch-clamp electrophysiology, applied to cones within the intact retina or isolated by enzymatic dissociation. We have established a logistical and technological framework that supplies us with foveal tissue and allows us to record from these delicate cells. Our proposed experiments constitute early steps toward a comprehensive understanding of the fovea at the level of cellular neurophysiology.
The World Health Organization estimates that forty million individuals are blind and, in developed nations, the leading cause is macular degeneration. The center of the macula is a structure called the fovea, where specialized cone photoreceptors initiate most visual awareness. Our goal is to understand the normal physiology of the foveal cones, which will help establish a baseline for diagnosing disease and provide a benchmark for evaluating clinical treatments
