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Updated: Jul 31, 2025
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Aging induces cell loss and a decline in phagosome processing in the mouse retinal pigment epithelium
Jessica Y W Ma1, Ursula Greferath1, Josephine H C Wong1
1Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia.
Abstract:
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and dysfunction in the retinal pigment epithelium (RPE) with age is known to contribute to disease development. The aim of this study was to investigate how the C57BL/6J mouse RPE changes with age. RPE structure was found to change with age and eccentricity, with cell size increasing, nuclei lost, and tight junctions altered in the peripheral retina. Phagocytosis of photoreceptor outer segments (POS) by the RPE was investigated using gene expression analysis and histology. RNA-Seq transcriptomic gene profiling of the RPE showed a downregulation of genes involved in phagosome processing and histological analysis showed a decline in phagosome-lysosome association in the aged tissue. In addition, failures in the autophagy pathway that modulates intracellular waste degradation were observed in the aged RPE tissue. These findings highlight that RPE cell loss and slowing of POS processing contribute to RPE dysfunction with age and may predispose the aging eye to AMD development.
Insights
Aging causes retinal pigment epithelium (RPE) cell loss and slows photoreceptor outer segment (POS) processing, contributing to age-related macular degeneration (AMD) and vision loss.
Area of Science:
- Ophthalmology
- Cell Biology
- Gerontology
Background:
- Age-related macular degeneration (AMD) is a primary cause of irreversible vision loss.
- Retinal pigment epithelium (RPE) dysfunction with age is a key factor in AMD development.
Purpose of the Study:
- To investigate age-related structural and functional changes in the C57BL/6J mouse RPE.
- To understand the molecular mechanisms underlying RPE aging and its link to AMD.
Main Methods:
- Histological analysis of RPE structure and cell morphology.
- RNA-Seq transcriptomic profiling to analyze gene expression.
- Assessment of phagocytosis and autophagy pathways in aged RPE.
Main Results:
- Aged RPE exhibited structural changes, including increased cell size and altered tight junctions, particularly in the peripheral retina.
- Downregulation of genes involved in phagosome processing and reduced phagosome-lysosome association were observed.
- Failures in the autophagy pathway were identified in aged RPE tissue.
Conclusions:
- RPE cell loss and impaired POS processing contribute to RPE dysfunction in aging.
- These age-related changes in RPE may increase susceptibility to AMD development.
