Studies are proposed to continue and extend findings relevant to the pathological effects of visible light in the eye and the mechanisms by which protective agents such as ascorbic acid reduce or prevent light damage. We will study different forms of retinal light damage, involving primarily degeneration of the visual cells, or damage to both the visual cells and the associated retinal pigment epithelium (RPE). Our long term goal is to understand the mechanism of light damage in the rat and, from the insights we gain, to extend our findings to other species. These studies are seen as being relevant to the prevention of light damage in the human eye, especially during periods of intense light exposure as may occur in the clinical, surgical or work-place environments and from the long term-cumulative effects of light in the eye. The protective effects of ascorbic acid administration and dietarily reduced levels of rod outer segment (ROS) docosahexaenoic acid will be studied separately, or in combination under conditions which accelerate and exacerbate different forms of light damage and during early discrete periods of light exposure to identify causative factors of damage. Reversible and irreversible effects of light will be determined by measuring rhodopsin and visual cell DNA, peroxidative metabolites of fatty acids and ERG changes in the retinas of rats. Retinol and enzyme measurements will be made to assess the effects of light's toxic action on the RPE and ROS membranes, in combination with collaborative histological evaluation. Monoclonal antibody based methods will be used to determine adaptive changes in the intracellular visual cell proteins transducin and S-antigen that may alter the form and extent of light damage in developing and adult rats. In general, the specific aims of our proposal are: (1) To determine the kinetics of the retinal uptake of D- and L-ascorbate following injection by different routes and to correlate the severity of damage with the concentration of ascorbate in the retina and RPE. (2) To correlate the magnitude of ROS degeneration, rod cell death and RPE degeneration as produced by intermittent light exposure with ROS polyunsaturated fatty acids and to isolate oxidative metabolites of labeled ROS fatty acids. (3) To measure the levels of rhodopsin, S-antigen and transducin in relation to long-term adaptive states in the retina and the expression of the rdy mutation, and to relate their levels to the light history dependent and age-related susceptibility of rats to damage from continuous or intermittent light exposure.
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