The primate retina is unusual among mammals in having a highly specialized central region, the fovea, which is formed by tightly-packed small cones, a displacement of the inner retina away from these cones, and a high concentration of ganglion cells which receive their input from the foveal cones. This organization is directly related to a high visual acuity characteristic of normal humans and monkeys. The peripheral retina has a complex topography formed by cone and rod photoreceptors (PR), with both cell types decreasing in spatial density with eccentricity. Rod and con circuits to ganglion cells in peripheral retina are still not well understood. How does this complex PR topography develop? When do inner retinal circuits become morphologically mature. The details of primate foveal development are gradually being revealed, in large prt due to the ready availability of well-preserved human and monkey retinal tissue available to our group at the University of Washington. In past years we have shown that both monkey and human fovea a long postnatal developmental maturation, and that cone spatial density increases with age, mainly due cell migration into the fovea. In this proposal we will continue to study primate fetal, infant and adult retinal morphology, using modern neuroanatomical techniques, to delineate the sequence of neuronal generation, neurotransmitter expression, and synaptic maturation in central vs peripheral retina. Our goal is to understand the cell types participating in the development of neuronal circuits, and to identify when cone rod circuits become mature. We also will examine whether neonatal visual deprivation affects any of these developmental parameters. Projects will include studies to show: 1) how PR cell size relates to changes in PR spatial density and retinal area; 2) how changes in foveal PR cell size, shape and density relate to visual performance; 3) what the distance is that PR migrate to cause the postnatal increase in foveal cone density; 4) when PR contain outer segment-related intracellular and extracellular molecules which are involved in phototransduction or vitamin A transport between PR and pigment epithelium; 5) when PR synapses are mature; 6) how the number, packing density, and size of pigment epithelial cells changes over development; 7) what effect visual deprivation has on PR development; 8) in what order neurotransmitter-specific inner retinal neurons are generated, and 9) how and when neurotransmitter-specific synaptic circuits develop in the retina.
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