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Updated: Mar 9, 2026
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
VISUALIZING RETINAL PIGMENT EPITHELIUM PHENOTYPES IN THE TRANSITION TO ATROPHY IN NEOVASCULAR AGE-RELATED MACULAR
Emma C Zanzottera1, Thomas Ach, Carrie Huisingh
1*Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama; †Department of Clinical Science ''Luigi Sacco,'' Eye Clinic, Sacco Hospital, University of Milan, Milan, Italy; ‡Department of Ophthalmology, University Hospital Würzburg, Würzburg, Germany; §Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; ¶Vitreous Retina Macula Consultants of New York, New York, New York; and **Department of Ophthalmology, New York University School of Medicine, New York, New York.
Purpose:
To enable future studies of retinal pigment epithelium (RPE) fate in the macular atrophy occurring in eyes with neovascular age-related macular degeneration (nvAMD), the authors determined how RPE morphology changes across the transition from health to atrophy in donor eyes with nvAMD.
Method:
In RPE-Bruch membrane flat mounts of 5 nvAMD eyes, the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histologic sections of 27 nvAMD eyes, RPE phenotypes were assessed at ±500 μm and ±100 μm from the descent of the external limiting membrane (ELM) toward the Bruch membrane. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE + BLamD were determined. Shapes of the ELM descent were recorded.
Results:
Approaching the ELM descent, the percentage of different RPE phenotypes and the thickness of RPE, BLamD, and RPE + BLamD each stayed roughly constant. Compared with a separately described cohort of eyes with geographic atrophy, eyes with nvAMD were more likely to have RPE dysmorphia that did not worsen toward the atrophy border, thinner BLamD overall (3.25 ± 3.46 μm vs. 7.99 ± 7.49 μm for geographic atrophy), and a higher proportion of oblique ELM descents (47.9 vs. 31.9%).
Conclusion:
The distribution of RPE phenotypes at the transition to macular atrophy in eyes with nvAMD differs from that in primary geographic atrophy, likely reflecting greater photoreceptor loss and the effects of exudation in nvAMD. This distribution, the shape of ELM descents, and thickness profiles may be useful metrics in clinical studies of macular atrophy using optical coherence tomography and fundus autofluorescence.
