Prion protein expression in mammalian lenses

Purpose. Aging and oxidative stress resulting from overexpression of Alzhei mer precursor protein (beta APP) have been studied as important factors con tributing 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 diseas es, and in rimmed vacuoles of IBM. Soluble beta-amyloid (Ab) fibrillar form s are now thought to play a critical role in and outside of cells by produc ing oxidative stress. In lens, beta APP and Ab increase in cultured lenses exposed to oxidative stress, and in areas of lens fiber cell degeneration i n thiamine (vitamin B1) deprived mice, a classic model of systemic oxidativ e stress. The purpose of the present study is to extend our studies of amyl oid disease-related protein expression in mammalian lenses. Methods. Western blot, immunohistochemical detection, and RT-PCR methods we re used to identify and quantitate prion protein expression in human, monke y, and guinea pig lenses. Results. We demonstrate for the first time that prion protein gene expressi on increases with oxidative stress in cultured human lens epithelial cells. In addition, we detected greater prion protein gene expression in fiber ce lls than epithelial cells in vivo. This is consistent with increases in pri on 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 o f lens fiber cell degeneration. Conclusions. The present data indicate that prion protein expression increa ses during lens development, and is substantially increased in cultured hum an lens epithelial cells exposed to oxidative stress. We also provide evide nce that prion protein immunoreactivity can be increased in regions of fibe r cell disorganization. These data suggest a potential role for prion prote in as a marker for some types of lens pathology, and in the mechanism of ox idative stress-related lens degeneration.