Cortical opacities constitute the majority of senile and sugar cataracts. The galactosemic cataract is a well studied model for sugar cataracts, while the Emory mouse cataract is a model for studies on senile-type cataracts. The objective of this proposal is to study the sequence of molecular events that occur during the initiation of these types of cataracts. These processes are assumed to develop in the epithelial cells, which later predispose the fiber cells to opacification. In particular, we plan to study the expected alterations in the expression of specific n RNAs during the early phase of induction of cataracts in two experimental cataract- development systems: in lenses from young rats fed galactose, and in lenses of the Emory mouse, all relative to their age-matched controls. We have already demonstrated that expression of the aldose reductase, the MP26, the gamma-crystallin and the c-myc mRNAs are transiently elevated to high levels within the first 24 hours following feeding of galactose to young rats. In the Emory mouse, we found the MP26 mRNA to decline at a high rate relative to its age-matched controls. These early alterations in mRNA levels that follow induction of cataracts support our basic premise that changes in epithelial cell metabolism in cataracts may be intensified by changes in the levels of expression of specific mRNAs. Our next objectives will be to study epithelial cell involvement in the initiation of cataracts induced both by hereditary (Emory mouse) and environmental (galactose) causes. Thus, levels of various epithelial cell- specific and fiber cell-specific mRNAs will be quantitated during the initial phase of development of galactosemic rat and Emory mouse cataract. Such an analysis will also include quantitation of the mRNAs for the various oxidation-protection enzymes that are expected to change during cataractogenesis in both the Emory mouse and in the galactosemic rat. Our study will determine whether underlying specific molecular events that occur in the epithelial cell precede fiber cell opacification. Eventually, we plan to determine whether similar phenomena occur in human lenses as they age or as they develop cataract. The methodology we are using includes contemporary molecular biology methods and immunoassay procedures for quantitating and visualizing the distribution of both the gene transcripts and their translational products in lens undergoing development of cataracts.
