Many amyloid diseases are characterized by protein aggregations linked to oxidative stress. Such diseases including those of the brain, muscle, and blood vessels exhibit plaques containing -amyloid (A). Here we demonstrate that Alzheimer's precursor protein (APP) and A are present at low levels in normal lenses and increase in intact cultured monkey lenses treated with HO or UV radiation (known cataractogenic agents), and with phorbol 12-myristate 13-acetate. AP-1 factor binding, shown by others to up-regulate APP expression, increased in the monkey lenses treated with HO, UV radiation, or phorbol 12-myristate 13-acetate and paralleled the increase in APP expression. Rat lenses exposed to oxidative stress showed increased APP in the anterior epithelium and cortex. Incubation of cultured rabbit lens N/N1003A epithelial cells with A induced inclusions and vacuoles and was cytotoxic. A cross-reacting protein was readily detected in the cortex of a cataractous human lens. Our data show that APP and A increase in mammalian lenses as part of a response to HO or UV radiation and suggest that they may contribute to the mechanism by which oxidative damage leads to lens opacification.

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