The studies described in this grant application raise the question of whether damage to epithelial cell DNA may be an initiating or early event in the development of maturity onset cataract. This hypothesis, in turn, is based on preliminary findings from our laboratory that suggest that DNA damage and repair are major aspects of the overall biology of the lens epithelium. Funds are requested to determine if an association exists between oxidation of lens DNA, and the development of lens opacities. Human lens epithelial cell DNA from normal individuals and from patients with cataract will be compared with respect to the degree and type of lens DNA damage and the effectiveness of DNA repair systems. In addition, the investigators will seek to establish and identify a link between the early expression of maturity onset cataract and as yet undefined genetic markers. The impact of oxidative stress upon lens epithelial cell DNA will also be examined by determining the relative susceptibility of various genetic loci to oxidative insult and by determining whether oxidative stress results in the induction of DNA repair enzymes and/or oxidative detoxifying systems. In addition, the effect of the state of expression of defined genes upon their relative susceptibility to DNA damage will be examined. Any association between DNA damage and the development of maturity onset cataract would have broad implications with respect to the treatment and prevention of lens opacities including but not limited to the development of antioxidant compounds effective in preventing DNA damage and mechanisms for stimulating the DNA repair activity in the lens.
| Kleiman, N J; Spector, A (1993) DNA single strand breaks in human lens epithelial cells from patients with cataract. Curr Eye Res 12:423-31 |
