Clinicopathological features of retinal glial and choroidal changes in an eye with multi-focal geographic atrophy.

Abstract

Purpose : Retinal Müller cell (MC) changes and choroidal pathology of an eye from a donor with multi-focal geographic atrophy (GA) and type 1 macular neovascularization (T1NV) was investigated using histology and immunohistochemistry. These features were correlated with clinical images.

Methods : The donor was followed clinically for five years with the last exam six years prior to death. Eyes were fixed in 4% paraformaldehyde (PFA) 5 hrs postmortem. Eyes were imaged ex vivo prior to storing in 1% PFA (PMID 37306417). Gross photographs were taken prior to dissecting the retina and choroid in half of the posterior pole as well as the superior nasal region. The remaining tissue was cryopreserved. Flatmount retina was immunolabeled with antibodies against glial fibrillary acidic protein (GFAP; activated MC and astrocytes) and glutamine synthetase (GS, MC) and Ulex europaeus (UEA) lectin (blood vessels). RPE/choroid was stained with zonula occludin 1 (ZO-1) and imaged before removing RPE and labeling with UEA lectin. Images were collected on a Zeiss 710 confocal microscope. The percent vascular area (%VA) was quantified using ImageJ. Results were compared to age-matched controls.

Results : Gross examination demonstrated RPE with a mottled appearance over presumably calcified drusen. In the atrophic area, a large glial membrane comprised of MC processes surrounded both drusen and outer retinal pigmented lesions. Retinal vessel density in the macula was reduced (14.3%VA) compared to age-matched controls (34%VA). Although visualization of the UEA lectin-stained choroidal vasculature was masked by thick basal laminar deposits, attenuation of the choriocapillaris (CC) was evident in the posterior pole. The choroidal %VA was 35% compared to 81% in age-matched controls. Surviving CC luminal diameters was reduced to 11 µm compared to 16 µm in controls. Choroidal venules and veins were congested throughout the posterior pole. CC attenuation was also noted in the superior choroid, adjacent to T1NV. Imaging of the corresponding retina with the photoreceptor side up revealed GFAP and vimentin-positive glial cell processes surrounding the UEA-lectin positive T1NV.

Conclusions : Clinical imaging and histology demonstrated congested and dilated large choroidal veins. MCs ensheath calcified drusen, T1NV and pigmented lesions throughout the retina, extending previous observations (PMID: 36862121, 30404862).

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.