ABNORMAL EXPRESSION OF ALDOSE REDUCTASE MESSENGER-RNA IN FIBER CELLS OF CATARACTOUS RAT LENS - ANALYSIS BY IN-SITU HYBRIDIZATION

Aldose reductase (AR), an enzyme of the polyol pathway, has been impli cated in the pathogenesis of diabetic and galactosemic cataracts. AR m RNA is a specific transcript of the lens epithelial cells. However, in addition to its presence at high levels in the epithelial cells at th e equator, it is also found at significant concentrations in fiber cel ls at the lens bow. In this study we extended our previous work, and e xamined the distribution of AR mRNA by in situ hybridization in lens o f rats maintained on a 50% galactose diet for up to 20 days, then reve rsed to a normal diet for an additional 20 days. It was found that wit hin 8 days on galactose the posterior AR mRNA dissipated, with no clea r increase in this transcript in the lens epithelial cells. By 16 to 1 7 days on galactose, the surviving fiber cells in the equatorial regio n appeared to express AR mRNA; these cells in the normal lens contain insignificant amounts of AR mRNA, as we have previously demonstrated. AR mRNA in the fiber cells of the cataractous lens appears to be of th e same base length as that found in the control, indicating that the A R mRNA in these cells may not represent a degraded transcript. Upon re versal of the cataracts, the posterior AR mRNA re-accumulates, and the fiber cells at the equator appear to have lost the AR mRNA that accum ulated during the period of exposure to galactose. The data demonstrat e that during formation of galactose-cataract, surviving cortical fibe r cells express significant levels of AR mRNA, while following withdra wal from galactose these fiber cells lose that activity.