A donor-age-dependent change in the activity of alpha-mannosidase in human cultured RPE cells

Six acidic glycosidase activities in cultured human retinal pigment epithelium (RPE) cells from donors of different ages (19 to 80 years) were studied with regard to pH optimum, Km, Vmax and specific activity. For alpha-mannosidase we found significant age-dependent decreases in specific activity and Vmax but not in Km. The other glycosidases and acid phosphatase, lactate dehydrogenase (LDH) and citrate synthase showed no change in these parameters with donor age. The alpha mannosidase activity of older donor cells could be activated almost 2-fold by the addition of zinc. This is the first report of age-dependent change in a human RPE lysosomal enzyme. Since alpha-mannosidase is probably required for the degradation of rhodopsin in the phagolysosomal system of the RPE, decrease in this enzyme activity may lead to accumulation of undigested rod outer segments (ROS) and drusen, both of which are associated with age-related macular degeneration (AMD).