Y. Wen et I. Bekhor, LEVELS OF EXPRESSION OF HEXOKINASE, ALDOSE REDUCTASE AND SORBITOL DEHYDROGENASE GENES IN LENS OF MOUSE AND RAT, Current eye research, 12(4), 1993, pp. 323-332
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 th
e 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 p
athway may lead to various diabetic complications, including a lesseni
ng of lens clarity. We have therefore determined the levels of express
ion 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 hybridiz
ation analysis, and by quantitation of the resulting hexokinase, aldos
e 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 on
ly approached about 1/4 that of the aldose reductase gene. The extent
of expression of the SDH gene, however, was equal between the mouse an
d rat lenses. These results were calculated relative to the level of e
xpression of the alphaA-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 mR
NAs relative to aldose reductase mRNAs in the lens would be expected t
o favor metabolism of glucose via the glycolytic pathway rather than t
he sorbitol pathway, leading to retardation of development of sugar ca
taracts in the mouse lens; while the opposite is true for the rat lens
.