Levels of expression of hexokinase, aldose reductase and sorbitol dehydrogenase genes in lens of mouse and rat.

Abstract

The level of expression of the genes for hexokinase, aldose reductase and sorbitol dehydrogenase was investigated in lenses of mice and rats. These genes represent two separate but interrelated pathways for the metabolism of glucose in the cell. It is hypothesized that the extent of expression of the hexokinase gene may play an important role in the regulation of the levels of glucose in the lens. It is known that if there occurs a build up of intracellular glucose, such as in diabetes mellitus, activation of the aldose reductase/sorbitol dehydrogenase pathway may lead to various diabetic complications, including a lessening of lens clarity. We have therefore determined the levels of expression of the genes for these three enzymes in the lens of both mice and rats. Mice are known to be more resistant than rats to the development of lens opacification during hyperglycemia. By Northern blot hybridization analysis, and by quantitation of the resulting hexokinase, aldose reductase and sorbitol dehydrogenase mRNA hybrids, we found that in the mouse lens the expression of the hexokinase gene exceeded that of the aldose reductase gene by a factor of three, while in the rat it only approached about 1/4 that of the aldose reductase gene. The extent of expression of the SDH gene, however, was equal between the mouse and rat lenses. These results were calculated relative to the level of expression of the alpha A-crystallin gene in those two types of lenses, in order to account for the generally higher genetic expression found in the rat relative to the mouse lens due to its higher content of DNA, henceforth larger mass. The presence of high levels of hexokinase mRNAs relative to aldose reductase mRNAs in the lens would be expected to favor metabolism of glucose via the glycolytic pathway rather than the sorbitol pathway, leading to retardation of development of sugar cataracts in the mouse lens; while the opposite is true for the rat lens.