Figure 9.

Summary diagram of Aβ-induced pathology in the retina. The age-related Aβ accumulation reported in sub-RPE/drusen, POS and choroid of donor AMD tissues and in animal models is recapitulated by Aβ-injected mice and by in vitro studies. (a) Development of localized retinal pathology with GA-like features alongside synaptic loss in the OPL following subretinal Aβ injection in living mouse eyes. (b) Impaired RPE barrier with development of contracted RPE foci following exposure to human oligomeric Aβ_1-42. (c) Choroidal pathology in the form of increased endothelial cell migration after Aβ exposure. Aβ effects appear to be mediated directly rather than via upregulation of VEGF. (d) Aβ is internalized by RPE lysosomes, which become swollen. An insufficient lysosomal cathepsin B response contributes to Aβ accumulating in RPE lysosomes. RPE exposed to oligomeric Aβ exhibit lysosomal deficits affecting the capacity to traffic/degrade POS cargos, which over time, could contribute to developing visual defects.