TRANSIENT ELEVATION OF ALDOSE REDUCTASE MESSENGER-RNA IN LENS OF RATS DEVELOPING GALACTOSE CATARACTS

Aldose reductase (AR), a major enzyme in the polyol pathway, is thought to be responsible for accumulation of polyols in lenses exposed to high doses of galactose or glucose, and it may be linked to some of the complications found in diabetes. In this report we examined the level of expression of AR mRNA in lens epithelia undergoing development of galactose cataracts in vivo. The AR mRNA was quantitated by Northern blot hybridization with a [S-35]-RNA transcript from a previously described AR cDNA clone. This was done on normal lens epithelia and on epithelia from lens of rats fed a diet of Purina Chow containing 50% galactose for periods of from 6 hr to 20 days. We found AR mRNA to elevate to about 5-fold the control levels by 12-24 hr on galactose, then decrease to the control levels by day 4. The increase in AR mRNA appears to be transitory. The high abundance in AR mRNA by 24 hr on galactose was confirmed by in situ hybridization. At later periods, from 8 to 20 days on galactose, a slow increase in AR mRNA took effect, as we have previously reported. Changes in the levels of galactose and dulcitol between 0 and 96 hr were also quantitated by gas chromatography, showing that there was a significant increase in both galactose and dulcitol occurring throughout the experimental period. The induction in mRNA accumulation in the lens epithelia within the first 12-24 hr does not appear to be specific for AR mRNA, but it is widespread and affects at least three other lens genes coding for: the gamma-crystallin, the lens intrinsic membrane protein MP26 and c-myc.