Abnormal expression of aldose reductase mRNA in fiber cells of cataractous rat lens. Analysis by in situ hybridization.

Abstract

Aldose reductase (AR), an enzyme of the polyol pathway, has been implicated in the pathogenesis of diabetic and galactosemic cataracts. AR mRNA is a specific transcript of the lens epithelial cells. However, in addition to its presence at high levels in the epithelial cells at the equator, it is also found at significant concentrations in fiber cells at the lens bow. In this study we extended our previous work, and examined the distribution of AR mRNA by in situ hybridization in lens of rats maintained on a 50% galactose diet for up to 20 days, then reversed to a normal diet for an additional 20 days. It was found that within 8 days on galactose the posterior AR mRNA dissipated, with no clear increase in this transcript in the lens epithelial cells. By 16 to 17 days on galactose, the surviving fiber cells in the equatorial region 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 the same base length as that found in the control, indicating that the AR mRNA in these cells may not represent a degraded transcript. Upon reversal of the cataracts, the posterior AR mRNA re-accumulates, and the fiber cells at the equator appear to have lost the AR mRNA that accumulated during the period of exposure to galactose. The data demonstrate that during formation of galactose-cataract, surviving cortical fiber cells express significant levels of AR mRNA, while following withdrawal from galactose these fiber cells lose that activity.