Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration.
To investigate antigenic and morphologic features of microglial and vascular elements in the neural retina associated with age-related macular degeneration (ARMD) compared with those features in age-matched normal and young adult retinas. Adult eyes (n = 97) were classified histopathologically into normal and ARMD-associated groups. Peroxidase imunohistochemical examination of retinal flatmounts was used to visualize major histocompatibility complex class II (MHC-II) immunoreactivity; the intensity and distribution of labeling were quantified by image analysis. In histochemical investigation, reduced nicotinamide-adenine dinucleotide phosphate diaphorase and glial fibrillary acidic protein or MHC-II double labeling were used to detect vascular changes in some preparations. An increase in the proportion of the retina (percentage of total area) expressing MHC-II immunoreactivity was observed in age-matched retinas compared with that seen in normal retinas. A significant increase (P < 0.05) in the percentage of area immunoreactive for MHC-II was observed, primarily on vascular elements, in retinas with incipient ARMD compared with the area affected in the age-matched group. Increased MHC-II immunoreactivity on vessels in the normal-aged group observed with confocal microscopy was associated with irregularities in the organization of astrocytes. Hypertrophy of retinal microglia was also apparent, although the intensity of microglial MHC-II immunoreactivity was not significantly different between groups. The results indicate that an increase in MHC-II immunoreactivity on retinal vascular elements is associated with normal aging. A further increase in MHC-II immunoreactivity on vascular elements and morphologic changes in microglia was associated with incipient ARMD. Immunologic responses in neural retinal microglia and vascular elements appear to be related to early pathogenetic changes in retinal pigment epithelium pigmentation and drusen formation.