Cellular Reorganization in the Human Retina during Normal Aging

PURPOSE: To characterize the nature and extent of neuronal reorganization in the human retina during normal aging. METHODS: Retinas of young (18-34 years old) and aged (68-77 years old) human donors were examined. Immunocytochemical methods and antibodies directed against Go-alpha, protein kinase C, parvalbumin, calbindin, calretinin, and choline acetyltransferase were used to stain different retinal cell types. Confocal images of retinal sections from the optic disc to the peripheral edge were taken at three eccentricities, and the density and length of cellular processes were quantified with neuroanatomical analysis software. RESULTS: Dendritic fibers of rod and On-cone bipolar cells were found to extend well beyond the normal boundary of the outer plexiform layer (OPL) into the outer nuclear layer (ONL) in aged retinas. Length and density of these elongated fibers were significantly greater in aged than in young retinas. This phenomenon demonstrated a clear spatial gradient that was most prevalent in the periphery and was infrequent in the central region of the retina. Horizontal cells, which normally make triad synaptic connections with photoreceptors and bipolar cells, also had dendrites that extended into the ONL in aged retinas, and these were spatially juxtaposed with the elongated dendrites of bipolar cells. CONCLUSIONS: Rod and On-cone bipolar cells, as well as horizontal cells of the human retina, undergo extensive dendritic reorganization during normal aging. Although literature on aging has tended to emphasize degenerative and regressive changes, the present findings provide evidence for a remarkable degree of cellular plasticity in the aged human retina.