Presenilin expression in the ocular lens

Abstract

PURPOSE. Mutations in the presenilin (PS) proteins account for the majority of early onset Alzheimer's disease (AD) cases, apparently by influencing the cleavage of the Alzheimer's disease protein (ßAPP) to form ß-amyloid (Aß), the major component of plaques in the brains of AD patients. We reported previously that AD proteins are expressed in mammalian lenses, and that ßAPP and Aß increased in the epithelium and outer cortex of lenses subjected to oxidative stress. This increase paralleled the increase in AP1 DNA binding activity, which has been shown to accompany proliferative oxidative stress responses. Both cataract and AD have been closely linked with oxidative stress; further, both AD and cataract occur in a majority of Down Syndrome individuals. Here we investigate the expression and post-translational processing of PS proteins in the ocular lens. METHODS. In situ hybridization, immuohistochemical detection and immunoblot assays were used to localize mRNA and proteins expression products and determine the approximate molecular weights of the resulting proteins in ocular tissue samples. RESULTS. We report here that PS protein and mRNA are expressed in lenses, and additionally in the cornea, and are proteolytically processed in a manner similar to that demonstrated in brain tissue. PS proteins and mRNAs were localized to the lens epithelium and outer fibers. This pattern agrees with the localization demonstrated by others for mammalian Notch-like receptor proteins. PS and Notch proteins occur together in developmentally regulated cascades of gene expression found in diverse biological systems. CONCLUSIONS. PS expression, together with ßAPP and Aß proteins, all associated with age-related degenerative disease, are expressed in lens and might contribute to cataractogenesis.