Müller Cell Changes and Subretinal Membrane Formation in an Eye With Multifocal Geographic Atrophy

Purpose: Müller cell 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 5 years, 6 years before death. The superior posterior pole retina of the right eye was dissected and immunolabeled with antibodies against glial fibrillary acidic protein (GFAP; activated Müller cells and astrocytes) and glutamine synthetase (GS; Müller cells) 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 Müller cell homeostatic and activation markers. Transmission electron microscopy (TEM) of the left eye was used to study ultrastructure changes. Results: Gross examination demonstrated mottled retinal pigment epithelium (RPE) over presumably calcified drusen. In the macular area, Müller cell processes surrounding both drusen and outer retinal pigmented lesions created a large subretinal membrane. Cryosection analysis demonstrated persistence of aquaporin 4 and GS in Müller cells 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 outer junctional zone. Cryosection labeling and TEM confirmed Müller cell 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. Müller cells penetrating basal laminar deposits and encasing calcified drusen suggests attempting clearing and/or protecting the retina from harmful contents.