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Editors Selection IGR 8-4
Basic Research: APP & amyloid-beta-depostion on RGC loss
Comment by Jonathan Crowston on:
22180 Amyloid-β deposits lead to retinal degeneration in a mouse model of Alzheimer disease, Ning A; Cui J; To E et al., Investigative Ophthalmology and Visual Science, 2008; 49: 5136-5143
Recent studies have hinted at common links in the pathogenesis of glaucoma and Alzheimer's disease, specifically that abnormal processing of amyloid precursor protein and amyloid-beta accumulation may contribute to RGC loss in glaucoma. Elevated amyloid precursor protein (APP) and amyloidbeta have been found in the retinal ganglion cell layer of ocular hypertensive rats as well as in the DBA/2J mouse model of glaucoma. In addition chronic elevation of IOP has also been shown to predispose to abnormal processing of APP predisposing to amyloid-beta deposition. Countering this is the lack of convincing data showing amyloid-beta deposits in the retinas of glaucomatous eyes, although Tau protein phosphorylation another biochemical change in AD brains has recently been shown. Ning et al. (1375) studied the retinal changes in two strains of double-mutant mice that harbor mutations in the presenilin (PS1) and APP gene. These mice are established models for Alzheimer's disease and develop characteristic AD-like amyloid beta deposits in the brain. Although mouse numbers were small and age-matched wildtype controls were available for one of the strains, the authors were able to show that the retinal ganglion cell layers in the double-mutant mice had amyloid-beta accumulation and APP over-expression which increased with age. Additionally, there were higher rates of apoptosis in the RGC layer and increased immunoreactivity to markers for microglial cells and monocytechemotactic protein. These changes are similar to histological changes in the Alzheimer's brain. These data suggest that mutations that predispose to abnormal processing of APP in the brain also lead to changes in the retina that are associated with accelerated death of retinal ganglion cells. A question that still remains is whether or not abnormal processing of APP and amyloid-beta deposition contributes to retinal ganglion cell loss in glaucoma.
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