Diabetes-induced vascular dysfunction in the retina: role of endothelins

Aims/hypothesis. Vasoactive factors like endothelins, by virtue of the micr ovascular regulation as well as by other effects, possibly play important p arts in the pathogenesis of diabetic retinal microangiopathy. We investigat ed retinal vascular dysfunction in streptozotocin-induced diabetes and its relation with endothelins in short- and long-term diabetes. Methods. Diabetic rats with or without an endothelin receptor antagonist (b osentan) treatment were investigated after 1 month and 6 months of follow-u p. Retinal blood flow was measured and compared with age- and sex-matched n on-diabetic control animals. Retinal tissues were analysed for endothelin-l . endothelin-3, endothelin A and endotherin B mRNA. Distribution of endothe lin-l and endothelin-3 was investigated by immunocytochemistry and that for endothelin receptors by ligand binding and autoradiography. Results. Diabetic animals showed hyperglycaemia, glycosuria, elevated glyca ted haemoglobin values and reduced body weight gain. Retinal blood flow sho wed an increased resistivity index, an indicator of vasoconstriction, after I month of diabetes which was prevented by treatment with bosentan. This f unctional change in diabetes was eliminated after 6 months of followup. The retina from the diabetic animals showed increased mRNA expression for endo thelin-l, endothelin-3 and endothelin A after one month. In addition, endot helin B mRNA expression was increased after 6 months. Furthermore, endothel in-l and endothelin-3 immunoreactivity and endothelin receptor concentratio ns were increased in the retina of diabetic rats. Conclusion/interpretation. The results from this study indicate that the en dothelin system is of importance in mediating retinal changes in diabetes a lthough mechanisms of the endothelin system alteration as well as their eff ects might vary depending on the duration of diabetes.