Mechanisms of Retinal Ganglion Cell Development in the Rhesus Macaque

At present, no effective treatments are known for many common neurological problems. For instance, degenerative diseases and central nervous system injuries are two examples of conditions for which few treatment options exist. Studying how neurons develop, and how they establish and maintain connections may provide important insights into potential treatment modalities. To this end, retinal ganglion cell structural development was studied in the fetal rhesus macaque ranging in age from embryonic day (E)60 to El65 (gestation is 165 ± 2 days). Horse radish peroxidase (HRP) retrograde labeling techniques were used to investigate changes in retinal ganglion cell structure during fetal development. To better understand the mechanisms of dendritic development and the establishment of neuron distributions, dendritic outgrowth in relation to the development of subclass and the formation of the regular distribution of ganglion cells were examined in Chapters Two and Three. The studies in Chapters Four and Five examined dendritic and axon morphology between centrally and peripherally located ganglion cells with respect to foveal formation. Dendritic development in the primate was found to be similar to but more precise than seen in other animal models. Additionally, the development of cell subclass was discovered to be an important component in the establishment of retinal ganglion cell mosaics. The studies comparing central and peripheral ganglion cells demonstrated that cells in the central retina migrate peripherally forming the foveal pit. Furthermore, arcuate fascicle development was shown to be mediated by differences in factors that influence axon outgrowth and guidance between cells located in the central and peripheral retina. These studies have provided several important implications for foveal development. First, the location of the fovea is set early in development as evidenced by the lack of areal growth between the future fovea and optic disk and the early avoidance of the central retina by outgrowing axons and ingrowing blood vessels. Moreover, the foveal pit is formed by the active migration of retinal ganglion cells from the center of the developing fovea and not solely from cell death or increases in intraocular pressure forcing the inner retinal layers peripherally. Keywords: Axon guidance; Fovea; Primate; Morphology, Mosaic