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PH Frederikse, G Li, X-O Ren, S Qazi, P Farnsworth; Fiber Cell Defects in a Human ß-amyloid (Aß) Transgenic Mouse Model of Alzheimer Pathophysiology in the Lens . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4801.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Alzheimer's disease (AD) pathophysiology contributes to loss of mental function and visual clarity that can occur during aging. Increased oxidative stress is linked with AD and cataract formation. Previously, we demonstrated AD pathophysiology in lenses and fiber cell degeneration in a model of acute systemic oxidative stress induced by thiamine (Vitamin B1) deprivation that also produces AD neuropathology. Using a genetic model of increased Alzheimer precursor protein (APP) gene dosage that occurs in Down Syndrome (trisomy 21) we demonstrated lens disorganization & degeneration. Recent data from others describe cataracts in a classic mutated APP transgenic model of AD neuro-pathophysiology due to extraneuronal expression by the prion promoter. Here, transgenic mice were engineered to express human ß-amyloid (hAß) specifically in the lens to examine hAß effects in isolation from the numerous and diverse biological activities of APP precursor protein functional domains. Methods: The lens specific αA-crystallin promoter was used to drive expression of hAß in lenses of transgenic mice. H & E staining, immunohistochemistry, and quantitative PCR were used to demonstrate lens defects, and to assay AD, tau and stress-related gene expression. Results: hAß expressed in the mouse lens produces posterior cataract and fiber cell degeneration with increased AD and stress-related gene expression. Conclusion: hAß expressed in lenses produces fiber cell degeneration and posterior cataracts related to oxidative stress. The present data extend our previous findings indicating AD pathophysiology related to oxidative stress occurs in the lens, and demonstrate a specific role for Aß in this process.
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