In continuing our investigation on the etiology and mechanism of opacity formation in mammalian lenses, we propose to 1) continue the studies on the protein alterations associated with the progression of cataractogenesis, particularly in the F-II protein, 2) study the development of the lens of neonatal rats; to produce galactosemic neonatal rats with cataracts and analyze the biochemical alteration of the lens proteins, and to test the possible reversibility of the galactosemic cataracts, 3) correlate our biochemical findings with the observations on the ultrastructure of the lens. It is hoped that these approaches will yield important information which will fulfill our research goal to determine experimentally the possibility of preventing, retarding or reversing cataractogenesis. The initial focus of our research endeavors has been and will be on the rat (and other animal) lens model system. Whenever our new approaches and experimental results on the animal model appear significant and applicable, extended experiments will be carried out in human lens. Experimental methods to be used to achieve the specific aims mentioned above are as follows: 1) Further investigation of the characteristics of the F-II protein will be made by improving the isolation and purification procedures, including HPLC. By chemical modification and analysis of the protein, the primary sequence of the polypeptide(s) is expected to be determined. 2) Investigation is to be continued on development of the rat and human lenses and cataracts; the effect of galactose diet on neonatal rat lens will continue to be a major topic. Hypermature rat and human cataractous lenses will be further studied in detailed fashion. The effect of prostaglandin on cataractogenesis will also be determined. 3) Investigation will be continued on the correlation of the biochemical parameters measured and the ultrastructural modifications of the lenses, particularly during cataractogenesis. It is further hoped that the basic scientific findings from this laboratory and others will provide essential information and a foundation for new clinical applications and advances by which mankind will be benefited. *F-II protein exists in normal rat and human lenses, appx. 20%, but diminishes with progression of cataractogenesis.
