PRESENILIN EXPRESSION IN THE OCULAR LENS

Purpose. Mutations in the presenilin (PS) proteins account for the maj ority of early onset Alzheimer's disease (AD) cases, apparently by inf luencing the cleavage of the Alzheimer's disease protein (beta APP) to form beta-amyloid (A beta), the major component of plaques in the bra ins of AD patients. We reported previously that AD proteins are expres sed in mammalian lenses, and that beta APP and A beta increased in the epithelium and outer cortex of lenses subjected to oxidative stress. This increase paralleled the increase in AP1 DNA binding activity, whi ch has been shown to accompany proliferative oxidative stress response s. Both cataract and AD have been closely linked with oxidative stress ; further, both AD and cataract occur in a majority of Down Syndrome i ndividuals. Here we investigate the expression and post-translational processing of PS proteins in the ocular lens. Methods. In situ hybridi zation, immuohistochemical detection and immunoblot assays were used t o localize mRNA and proteins expression products and determine the app roximate molecular weights of the resulting proteins in ocular tissue samples. Results. We report here that PS protein and mRNA are expresse d in lenses, and additionally in the cornea, and are proteolytically p rocessed in a manner similar to that demonstrated in brain tissue. PS proteins and mRNAs were localized to the lens epithelium and outer fib ers. This pattern agrees with the localization demonstrated by others for mammalian Notch-like receptor proteins. PS and Notch proteins occu r together in developmentally regulated cascades of gene expression fo und in diverse biological systems. Conclusions. PS expression, togethe r with beta APP and A beta proteins, all associated with age-related d egenerative disease, are expressed in lens and might contribute to cat aractogenesis.