REGULATION OF GROWTH-FACTOR MESSENGER-RNA LEVELS IN THE EYES OF DIABETIC RATS

The underlying etiology of diabetic microvascular disease remains unkn own. To examine the potential contribution of basic fibroblast growth factor (bFGF), which is an angiogenic factor, and insulin-like growth factor-I (IGF-I) to the development of diabetic microvascular disease, bFGF and IGF-I mRNA levels were measured in tissues of control, diabe tic, and insulin-treated diabetic rats. Diabetes was induced in rats b y intravenous injection of streptozotocin (STZ) 65 mg/kg, and the rats were maintained for 21 days. bFGF mRNA levels increased threefold in the eyes of diabetic versus control rats, whereas a consistent change in bFGF mRNA levels was not observed in other tissues. In contrast, IG F-I mRNA levels decreased in the eyes and other tissues, including kid ney, lung, and skeletal muscle, of diabetic as compared with control r ats. Insulin treatment prevented the diabetes-induced increase in bFGF and decrease in IGF-I mRNA levels. Acidic FGF (aFGF) mRNA levels were unchanged in eyes from diabetic versus control rats. In partially pur ified retinas, diabetes increased bFGF mRNA levels twofold as compared with levels in control retinas, whereas IGF-I mRNA levels decreased t o 58% of control levels in retinas from diabetic rats. Insulin treatme nt again prevented the diabetes-induced increase in IGF-I mRNA levels in the retina but had no effect on the diabetes-induced increase in bF GF mRNA levels. bFGF peptide levels were minimally increased in diabet ic versus control retinas. Treatment of diabetic rats with the aldose reductase inhibitor sorbinil prevented the diabetes-induced increase i n sorbitol accumulation and myo-inositol depletion in the lens, but it did not affect the diabetes-induced increase in bFGF and decrease in IGF-I mRNA levels in the retina. Induction of hypoinsulinemia by fasti ng the animals did decrease IGF-I mRNA levels but did not reproduce th e diabetes-induced increase in bFGF mRNA levels in the eye. In conclus ion, these data demonstrate that the effect of diabetes on growth fact or mRNA levels in the eye is gene-specific, suggest that different met abolic abnormalities are responsible for diabetes-induced alterations in the production of different growth factors in the eye, and are cons istent with a role for bFGF in the development of diabetic retinopathy . Copyright (C) 1995 by W.B. Saunders Company