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Updated: Mar 3, 2026
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Dry age-related macular degeneration like pathology in aged 5XFAD mice: Ultrastructure and microarray analysis
Sung Wook Park1, Sora Im2, Hyoung Oh Jun3
1Department of Biomedical Sciences, Seoul National University College of Medicine, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea.
Abstract:
Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The two types of AMD are: dry and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD, there is no established mouse model that fully recapitulates the cardinal features of dry AMD. A lack of appropriate mouse model for dry AMD has hampered the translational research on the pathogenesis of the disease and the development of therapeutic agents. We hypothesized that 5XFAD mice, an animal model for the study of Alzheimer's disease, can be used as a mouse model for dry AMD with regard to the amyloid beta (Aβ) related pathology. In this study, the ultrastructure of the retinal pigment epithelium (RPE) of 5XFAD mice was analyzed using transmission electron microscopy. Of importance, the aged 5XFAD mice show ultrastructural changes in the RPE and Bruch's membrane (BM) that are compatible with the cardinal features of human dry AMD, including a loss of apical microvilli and basal infolding of the RPE, increased BM thickness, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laden phagosomes. In microarray-based analysis, the RPE complex of the aged 5XFAD mice shows differential gene expression profiles consistent with dry AMD in the inflammation response, immune reaction pathway, and decreased retinol metabolism. Taken together, we suggest that aged 5XFAD mice can be used as a mouse model of dry AMD to study Aβ related pathology and develop a new therapeutic approaches.
Insights
Aged 5XFAD mice exhibit retinal changes mimicking human dry age-related macular degeneration (AMD). This Alzheimer's disease model shows potential for studying AMD pathogenesis and developing new therapies.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Age-related macular degeneration (AMD) is a major cause of vision loss in older adults, with dry AMD lacking a fully representative animal model.
- Current research into dry AMD pathogenesis and therapeutics is hindered by the absence of suitable animal models.
- Alzheimer's disease models, such as 5XFAD mice, are being explored for their potential relevance to other neurodegenerative conditions.
Purpose of the Study:
- To evaluate aged 5XFAD mice as a potential animal model for dry age-related macular degeneration (AMD).
- To investigate the amyloid beta (Aβ) related pathology in the retinal pigment epithelium (RPE) and Bruch's membrane (BM) of 5XFAD mice.
- To assess the suitability of 5XFAD mice for studying dry AMD mechanisms and therapeutic development.
Main Methods:
- Transmission electron microscopy was used to analyze the ultrastructure of the RPE and BM in aged 5XFAD mice.
- Microarray-based analysis was performed to examine gene expression profiles in the RPE complex.
- Histopathological features were compared to the cardinal signs of human dry AMD.
Main Results:
- Aged 5XFAD mice displayed RPE and BM ultrastructural changes consistent with dry AMD, including loss of RPE microvilli, thickened BM, basal deposits, and accumulation of lipofuscin.
- Gene expression analysis revealed differential profiles in inflammation response, immune pathways, and retinol metabolism, aligning with dry AMD characteristics.
- These findings suggest a strong correlation between Aβ pathology in 5XFAD mice and key features of human dry AMD.
Conclusions:
- Aged 5XFAD mice represent a promising new model for studying the Aβ-related pathology of dry age-related macular degeneration (AMD).
- This model can facilitate research into the pathogenesis of dry AMD and the development of novel therapeutic strategies.
- The 5XFAD mouse model offers a valuable platform for advancing translational research in AMD and Alzheimer's disease.
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