Müller cell changes and subretinal membrane formation in an eye with multifocal geographic atrophy

Abstract Purpose Müller cell (MC) morphology and markers were investigated using histology and immunohistochemistry in an eye with clinically documented multifocal geographic atrophy (GA) and correlated with clinical images. Methods The donor was followed clinically for five years and last examined six years before death. The superior posterior pole retina was dissected and immunolabeled with antibodies against glial fibrillary acidic protein (GFAP; activated MCs and astrocytes) and glutamine synthetase (GS, MC) and Ulex Europaeus Agglutinin-1 lectin (blood vessels) before embedding for JB-4 cross section analysis. The inferior macula was cryopreserved. Cryosections were immunolabeled with MC homeostatic and activation markers. Transmission electron microscopy (TEM) of the fellow eye was used to study ultrastructure changes. Results Gross examination demonstrated mottled retinal pigment epithelium (RPE) over presumably calcified drusen. In the submacular retina, MC processes surrounding both drusen and outer retinal pigmented lesions created a large subretinal membrane. Cryosection analysis demonstrated persistence of aquaporin 4 and GS in MCs with both proteins prominently expressed in the subretinal membrane. Increased MC S100B and GFAP expression were also observed in the atrophic area as well as the OJZ. Cryosection labeling and TEM confirmed the MC encasing calcified drusen and RPE debris as well as invading basal laminar deposits. Conclusions This multifocal GA case demonstrates how MC activation and structural changes surrounding individual drusen could coalesce, contributing to photoreceptor loss. MCs penetrating basal laminar deposits and encasing calcified drusen suggests that they are attempting to clear these and/or protect the retina from harmful contents.