Increased lenticular aldose reductase activity and high incidence of congenital cataract in the offspring of diabetic rats

Abstract

In previous experimental studies we have found a 47% incidence of congenital cataracts among the fetuses of manifestly diabetic (MD) rats, and 4% of the offspring of normal (N) rats. The aim of the present study was to clarify the role of the sorbitol shunt in the pathogenesis of this congenital defect. Light microscopical evaluation of the fetal lenses revealed excessive formation of vacuoles in offspring of MD rats compared to N offspring. On gestational day 16 we found that aldose reductase (AR) activity was doubled in the lenses of fetuses of MD rats as compared to that of N fetuses. This difference as well as the net activity of AR declined in both groups during subsequent development. The sorbitol concentration was elevated more than ten-fold in the MD fetal lenses compared to N fetal lenses at all time points. The sorbitol concentration in both the MD and the N group decreased from day 16 to day 20 and increased again slightly on day 22. We conclude that the diabetic uterine milieu induces elevated AR activity and sorbitol formation in the fetal lens. This over-activity of the sorbitol shunt may produce metabolic and osmotic imbalances in the fetal lens, resulting in excessive vacuole formation and subsequent development of congenital cataract.

Stres oksydacyjny indukowany hiperglikemią w cukrzycy ciążowej (GDM)

“…Maternal hyperglycaemia has been shown to cause a rise in sorbitol concentration in foetal tissue and AR activity in the lenses of diabetic rat foetuses [21,22]. Alterations in the polyol pathway have also been found in diabetic complications such as cardiomyopathy, neuropathy, nephropathy, and retinopathy [20].…”

Brain damage and congenital cataract due to autogenously fecal peritonitis in pregnant Wistar rats

“…As regard to experimental model of this disease, it is well recognized that congenital cataract is present in over 45% of the offspring of diabetic rats 13 retinopathy. This phenomenon can be studied in rat model 20 .…”