MODULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION INRETINAS WITH AGE-RELATED MACULAR DEGENERATION

Purpose. To investigate antigenic and morphologic features of microgli al and vascular elements in the neural retina associated with age-rela ted macular degeneration (ARMD) compared with those features in age-ma tched normal and young adult retinas. Methods. Adult eyes (n = 97) wer e classified histopathologically into normal and ARMD-associated group s, Peroxidase immunohistochemical examination of retinal flatmounts na s used to visualize major histocompatibility complex class II (MHC-II) immunoreactivity; the intensity and distribution of labeling were qua ntified by image analysis. In histochemical investigation, reduced nic otinamide-adenine dinucleotide phosphate diaphorase and glial fibrilla ry acidic protein or MHC-II double labeling were used to detect vascul ar changes in some preparations. Results. An increase in the proportio n of the retina (percentage of total area) expressing MHC-II immunorea ctivity was observed in age-matched retinas compared with that seen in normal retinas. A significant increase (P < 0.05) in the percentage o f area immunoreactive for MHC-II was observed, primarily on vascular e lements, in retinas with incipient ARMD compared with the area affecte d in the age-matched group. Increased MHC-II immunoreactivity on vesse ls in the normal-aged group observed with confocal microscopy was asso ciated with irregularities in the organization of astrocytes. Hypertro phy of retinal microglia was also apparent, although the intensity of microglial MHC-II immunoreactivity was not significantly different bet ween groups. Conclusions. The results indicate that an increase in MHC -II immunoreactivity on retinal vascular elements is associated with n ormal aging. A further increase in MHC-II immunoreactivity on vascular elements and morphologic changes in microglia was associated with inc ipient ARMD. Immunologic responses in neural retinal microglia and vas cular elements appear to be related to early pathogenetic changes in r etinal pigment epithelium pigmentation and drusen formation.