The human lens is continually under photooxidative and oxidative stress. Although light has been implicated in long term changes in the human lens that lead to aging and cataractogenesis, almost nothing is known concerning the actual role of light in those processes, the mechanism by which it occurs and the mechanism by which changing environmental conditions modify those reactions. The experiments outlined here will provide important, basic information concerning those processes. This is an especially timely question since some of the wavelengths of light filtered by the ozone layer are those that are absorbed by the human lens. Decreases in atmospheric ozone would increase photochemical stress on the lens. The effect of light on human lens will be thoroughly investigated by first corroborating the suggestion that the correlation between light and cortical cataracts is due to the focusing of the cornea on the inferonasal portion of the lens. A model cornea backed by photosensitive paper will be used to determine the spatial distribution of light impinging on the lens. Other goals are the development of an action spectrum for the constituents of the human lens. This presents the relative photochemical damage as a function of wavelength impinging on the sample. From these studies the PI will ascertain the wavelengths of light that must be filtered out in order to minimize damage to the human lens. Finally, the role of light in the specific molecular changes that occur in the human lens with age and cataractogenesis will be defined as well as the mechanism by which they were formed. These will be accomplished by the direct detection of active oxygen species and the structural identification the resultant photoproducts. These studies will give the absorbing species that initiate photochemical reactions in the lens, determine if there is a change in that sensitivity with age and determine the mechanism by which that damage occurs. This type of multidimensional approach has the best chance of elucidating the role of various photooxidative and oxidative processes in aging and cataractogenesis in the human lens and develop methods to retard those changes.
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