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Updated: Feb 17, 2026
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in
Sandrine Joly1, Simon Lamoureux1, Vincent Pernet1
1CUO-Recherche, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada.
Abstract:
Vision declines during normal aging and in Alzheimer's disease (AD). Although the toxic role of amyloid beta (Aβ) has been established in AD pathogenesis, its influence on the aging retina is unclear. Using APPswe/PS1ΔE9 transgenic (TG) mice, a classical AD model, the retinal cell function and survival was assessed by electroretinogram (ERG) recordings and immunofluorescent stainings. Strikingly, photopic ERG measurements revealed that the retinal response mediated by cones was preserved in aging TG mice relative to WT controls. In contrast to the cortex, the expression of mutated APPswe and PS1ΔE9 did not allow to detect Aβ or amyloid plaques in 13-month-old male TG retinae. In addition, the CTFβ/CTFα ratio was significantly lower in retinal samples than that in cortical extracts, suggesting that the nonamyloidogenic pathway may endogenously limit Aβ formation in the retina of male mice. Collectively, our data suggest that retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging.
Insights
Alzheimer's disease (AD) models show preserved cone vision in aging mice. Retinal amyloid processing may protect against vision loss, suggesting a unique protective mechanism in the aging eye.
Area of Science:
- Neuroscience
- Ophthalmology
- Gerontology
Background:
- Normal aging and Alzheimer's disease (AD) are associated with vision decline.
- The role of amyloid beta (Aβ) in AD pathogenesis is known, but its effect on the aging retina is unclear.
Purpose of the Study:
- To investigate the impact of AD-related genetic mutations on retinal cell function and survival.
- To determine if amyloid processing in the retina differs from the brain and influences vision during aging.
Main Methods:
- Utilized APPswe/PS1ΔE9 transgenic (TG) mice, a standard AD model.
- Assessed retinal function using electroretinogram (ERG) recordings.
- Examined retinal cell survival via immunofluorescent stainings.
Main Results:
- Photopic ERG revealed preserved cone-mediated retinal responses in aging TG mice compared to wild-type (WT) controls.
- Amyloid beta (Aβ) plaques and mutated APP/PS1 were not detected in the retinae of 13-month-old male TG mice.
- A lower CTFβ/CTFα ratio in retinal samples suggested a dominant nonamyloidogenic pathway limiting Aβ formation.
Conclusions:
- Retinal-specific amyloid processing may offer protection against AD-related vision impairment.
- Cone-dependent vision appears selectively preserved in aging mice with AD genetic models.
- The nonamyloidogenic pathway might play an endogenous protective role in the aging retina.
