Regulation of growth factor mRNA levels in the eyes of diabetic rats☆

Abstract 

The underlying etiology of diabetic microvascular disease remains unknown. To examine the potential contribution of basic fibroblact 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, diabetic, and insulin-treated diabetic rats. Diabetes was induced in rats by 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, IGF-I mRNA levels decreased in the eyes and other tissues, including kidney, lung, and skeletal muscle, of diabetic as compared with control rats. 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 purified retinas, diabetes increased bFGF mRNA levels twofold as compared with levels in control retinas, whereas IGF-I mRNA levels decreased to 58% of control levels in retinas from diabetic rats. Insulin treatment again prevented the diabetes-induced increase in IGF-I mRNA levels in the retina but had no effect on the diabetes-induced increase in bFGF mRNA levels, bFGF peptide levels were minimally increased in diabetic versus control retinas. Treatment of diabetic rats with the aldose reductase inhibitor sorbinil prevented the diabetes-induced increase in 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 mFINA levels in the retina. Induction of hypoinsulinemia by fasting the animals did decrease IGF-I mRNA levels but did not reproduce the diabetes-induced increase in bFGF mRNA levels in the eye. In conclusion, these data demonstrate that the effect of diabetes on growth factor mRNA levels in the eye is gene-specific, suggest that different metabolic abnormalities are responsible for diabetes-induced alterations in the production of different growth factors in the eye, and are consistent with a role for bFGF in the development of diabetic retinopathy.

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