Retinal ultrastructure of 5XFAD mice as an animal model of dry age-related macular degeneration

Abstract

Purpose : The study of dry age-related macular degeneration (AMD) has been hampered by a lack of proper animal models. Intracellular amyloid beta (Aβ) in retinal pigment epithelium (RPE) has been implicated in the pathogenesis of age-related macular degeneration. This study is aimed to demonstrate that 5XFAD mice, an animal model of Alzheimer’s disease producing high level of Aβ₄₂, develop cardinal features of AMD.

Methods : To evaluate retinal ultrastructure of 5XFAD mice, eyes from 5XFAD and age-matched wild-type mice, ranging from 9 to 12 months of age, were extensively examined histopathologically under electron microscope. RPE/choroid/scleral complexes were flat-mounted and immunostained with anti-Aβ and ZO-1 antibodies. Paraffin-embedded eye blocks were cross sectioned and stained with Sudan B black to evaluate lipofuscin granules. Aβ₄₂ level in RPE/choroid/scleral complex was measured using human Aβ₄₂ ELISA kit.

Results : Intracellular Aβ₄₂ was found concomitantly with RPE hypertrophy in 5XFAD mice. We also presented evidence that elevated Aβ₄₂ level in RPE/choroid/scleral complex of aged 5XFAD mice. 5XFAD mice recapitulated cardinal features of dry-AMD including drusenoid deposits, increased granules and lipofuscin, loss of apical microvilli and basal infolding, and thickened Bruch’s membrane. Intriguingly, choroid was filled with abundant melanocytes but less choriocapillaris vessels.

Conclusions : Eyes of 5XFAD mice showed retinal ultrastructure compatible with cardinal features of dry AMD. Thus, 5XFAD mice implicate Aβ related RPE dysfunction in AMD pathogenesis and may be useful as an animal model of dry AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.