Purpose. As senile cataracts and Alzheimer's senile dementia (AD) are diseases of protein aggregation linked to oxidative stress, we investigated cataract as an amyloidogenic disease involving AD proteins. Methods. Classic AD pathology stains (Congo red and Thioflavine T and S) were used to characterize amyloid in normal and cataractous lenses, together with immunohistochemical detection of AD proteins. Results. Previously we demonstrated that βAPP and Aβ increased in the epithelium and cortex of intact monkey and rat lenses treated with H2O2 or UV radiation. Incubation of lens epithelial cells with Aβ (1-40) or (25-35) produced vacuoles and was cytotoxic. Here we demonstrate the utility of classic AD stains to investigate a third aspect of amyloid disease: protein structure. Congo Red and fluorescent Thioflavine T and S stains react with the central region (nucleus) of mouse, guinea pig, jellyfish, and human lenses, indicating that higher order β-sheet structure is part of the normal lens. We detected abnormal Congo red, Thioflavine T and S staining in the lens cortex of a congenital C-crystallin guinea pig cataract, suggesting that these stains might be routinely used to investigate amyloid in both normal and cataractous lenses. Vacuoles (a hallmark of several types of cataract formation), amyloid staining, and Aβ, co-localize to regions of the cataractous lens cortex within portions of the elongated cells that contain the cellular nucleus in heterozygous C-crystallin guinea pigs. Conclusions. Our results indicate: 1) that higher order β-sheet structure is part of the normal lens nucleus and 2) that Aβ, AD-type amyloid and vacuole production in the lens cortex is part of an inappropriate proliferative response to oxidative stress, and contributes to the mechanism by which oxidative damage leads to decreased cell viability and ultimately to lens opacification.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience