The long-term objective of the proposed project is to evaluate functional changes in the tissues of the macular region of the retina to determine why the macula is pre-disposed to degenerative disease. On the assumption that an accelerated impairment in function of the retinal pigment epithelium (RPE) of the macula with age might contribute to age-related maculopathy, the specific aim of this proposed project is to develop an in vitro model to compare some basic cellular activities of macular and extramacular RPE with aging. Cell cultures will be propagated from RPE taken from specific retinal regions - the macula and the peripheral retina - of human eyes from donors of varying ages and from calf and adult bovine eyes. Using these cultures, both age-related and regional differences in the following functions of RPE will be evaluated: (1) the ability to phagocytize photoreceptor outer segments (by analysis of the internalization of nonspecific particles and of rod outer segments); (2) the ability to degrade the contents of phagosomes (by measurement of lysosomal enzyme activity); and (3) the ability to maintain the ionic environment of the photoreceptors (by quantitation of ion transport pump sites and measurement of pump activity). "Aging" will also be evaluated in the regional RPE cell cultures. Based on the observation that growth rates in vitro decline with both donor age with with senescence in vitro, the fraction of cycling cells will be measured in paired macular and extramacular RPE cultures. Culture media will also be assessed for the appearance of some putative age-specific secretory proteins. Age-related degeneration of the macula is the major cause of blindness among older individuals. It is difficult to develop therapies for this condition because of a lack of information about specializations of tissues at the macula and about changes in tissue function with aging. The proposed project is aimed at examining some topographical and age-related differences in RPE activity.
NIH ExPorter
NIH ExPorter