Prion protein expression in mammalian lenses

Abstract

Purpose. Aging and oxidative stress resulting from over-expression of Alzheimer precursor protein (ßAPP) have been studied as important factors contributing to the major age-related (sporadic), and minor (hereditary) forms of Alzheimer's disease (AD), and muscle inclusion body myositis, (IBM). AD and prion proteins accumulate in plaques linked with AD and scrapie diseases, and in rimmed vacuoles of IBM. Soluble ß-amyloid (Aß) fibrillar forms are now thought to play a critical role in and outside of cells by producing oxidative stress. In lens, ßAPP and Aß increase in cultured lenses exposed to oxidative stress, and in areas of lens fiber cell degeneration in thiamine (vitamin B1) deprived mice, a classic model of systemic oxidative stress. The purpose of the present study is to extend our studies of amyloid disease-related protein expression in mammalian lenses. Methods. Western blot, immunohistochemical detection, and RT-PCR methods were used to identify and quantitate prion protein expression in human, monkey, and guinea pig lenses. Results. We demonstrate for the first time that prion protein gene expression increases with oxidative stress in cultured human lens epithelial cells. In addition, we detected greater prion protein gene expression in fiber cells than epithelial cells in vivo. This is consistent with increases in prion protein expression demonstrated in myoblasts and neuronal cells induced to differentiate. Our initial investigations of prion protein in human lens cataracts identified increased prion protein immunoreactivity in regions of lens fiber cell degeneration. Conclusions. The present data indicate that prion protein expression increases during lens development, and is substantially increased in cultured human lens epithelial cells exposed to oxidative stress. We also provide evidence that prion protein immunoreactivity can be increased in regions of fiber cell disorganization. These data suggest a potential role for prion protein as a marker for some types of lens pathology, and in the mechanism of oxidative stress-related lens degeneration.