The Influence of Alloxan-Induced Diabetes on Müller Cell Contraction-Promoting Activities in Vitreous

Abstract

Previous studies from this laboratory revealed that vitreous insulin-like growth factor biological activity increases in diabetes and that this change can precede the onset of proliferative diabetic retinopathy. The goal of this study was to characterize this phenomenon in an animal model of alloxan-induced diabetes. Swine made diabetic with intravenous alloxan were euthanized at times varying from 0 to 90 days. Vitreous samples from normal and diabetic swine were evaluated for changes in Müller cell contraction-promoting activity, the presence of insulin-like growth factor binding protein (IGFBP), and carbonic anhydrase-I and -II. Ocular tissues from these animals were also evaluated for changes in contraction-promoting growth factors and IGFBP message levels. Alloxan-induced diabetes is associated with significant increases in vitreous Müller cell contraction-promoting activity that are present in as few as 30 days and are sustained for at least 90 days. Biochemical studies revealed that the increases cannot be attributed to loss of growth factor-attenuating IGFBPs, changes in local expression of contraction-promoting growth factors, or vitreous hemorrhage. The previously reported increases in Müller cell contraction-promoting activity detected in human diabetic vitreous are present in diabetic swine within 30 days of chemical induction. The increase does not appear to be attributable to loss of growth factor control, increases in local growth factor expression, or vitreous hemorrhage, suggesting that other mechanisms are involved. It is the authors' speculation that diabetes induces blood-vitreous barrier changes that allow a different subset of plasma proteins to enter vitreous fluids.