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Updated: Mar 22, 2026
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Detecting Aβ deposition and RPE cell senescence in the retinas of SAMP8 mice
Le Feng1, Lining Cao1, Yao Zhang1
1Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Aim:
Our previous study indicated that Aβ-induced Retinal Pigment Epithelial (RPE) cell senescence may be associated with chronic inflammation in age-related macular degeneration (AMD). The present study was designed to explore whether Aβ deposition and RPE senescence could be found in the senescence-prone mouse strain 8 (SAMP8), which is an animal model for AMD.
Methods:
Eyes of both SAMP8 and age-matched SAMR1 (SAM resistant) mice were examined in vivo by fundus photography and electroretinography (ERG). Retinal morphological features were assessed using light and electron microscopy. Aβ deposition and p16-positive senescent RPE cells were traced using immunofluorescence labeling. P16 expression was detected using western blot. Expressions of IL-6 and IL-8 in RPE/choroid were analyzed using RT-PCR.
Results:
In fundus of SAMP8, age-dependent increase of drusen-like lesions and the increase of granular autofluorescent spots were respectively detected using IR (near-infrared) and AF (autofluorescence) imaging of confocal scanning laser ophthalmoscope. The amplitude of the ERGs declined with age in SAMP8 and these changes were paralleled with the significant changes in retinal morphological features examined by funduscopy. Histopathological analysis found significant loss of photoreceptor outer segments (OS) and abnormal localization of RPE cells in aged SAMP8 mice. Degenerative changes in RPE cells of aged SAMP8 mice, including massive vacuoles, thickened Bruch's membrane (BrM), and loss of basal infoldings were further confirmed by electron microscopy. Increased Aβ deposits in OS layer and p16-positive senescent RPE cells were observed using immunofluorescence microscopy. Western blot confirmed that P16 expression was significantly increased in RPE cells of aged SAMP8 mice. Expressions of proinflammatory IL-6 and IL-8 were significantly upregulated in RPE/choroid of aged SAMP8 mice.
Conclusions:
Our results showed that aged SAMP8 mice developed ocular pathology similar to some features of human AMD. In this AMD mouse model, Aβ deposition and RPE senescence may be associated with AMD development, and RPE senescence is likely a mechanistic link between Aβ deposition and inflammation.
Insights
Amyloid-beta (Aβ) deposition and retinal pigment epithelial (RPE) cell senescence are linked to age-related macular degeneration (AMD) development. This study confirms Aβ and RPE senescence in an AMD mouse model, suggesting RPE senescence connects Aβ to inflammation.
Area of Science:
- Ophthalmology
- Gerontology
- Cell Biology
Background:
- Previous research linked amyloid-beta (Aβ)-induced retinal pigment epithelial (RPE) cell senescence to chronic inflammation in age-related macular degeneration (AMD).
- The senescence-prone mouse strain 8 (SAMP8) serves as a relevant animal model for studying AMD pathology.
Purpose of the Study:
- To investigate the presence of Aβ deposition and RPE senescence in the SAMP8 mouse model.
- To explore the potential association between Aβ deposition, RPE senescence, and inflammation in the context of AMD.
Main Methods:
- Fundus photography and electroretinography (ERG) were used for in vivo eye examinations.
- Retinal morphology was assessed via light and electron microscopy.
- Immunofluorescence, western blot, and RT-PCR were employed to detect Aβ deposition, p16 expression (a senescence marker), and inflammatory cytokines (IL-6, IL-8).
Main Results:
- SAMP8 mice exhibited age-dependent increases in drusen-like lesions and autofluorescent spots, alongside declining ERG amplitudes.
- Histopathology revealed photoreceptor outer segment loss, RPE cell abnormalities, and thickened Bruch's membrane in aged SAMP8 mice.
- Increased Aβ deposition, p16-positive senescent RPE cells, and elevated IL-6 and IL-8 expression were observed in aged SAMP8 mice.
Conclusions:
- Aged SAMP8 mice display ocular pathologies mirroring features of human AMD.
- Aβ deposition and RPE senescence are implicated in the development of AMD within this mouse model.
- RPE senescence appears to be a key mechanistic link connecting Aβ deposition to ocular inflammation in AMD.
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