ENDOTHELIN EXPRESSION IN OCULAR-TISSUES OF DIABETIC AND INSULIN-TREATED RATS

Purpose. The endothelins are potent vasoactive peptides that are widel y distributed in ocular tissues. There is evidence linking the endothe lins to vascular dysfunction in diabetic microangiopathy. Thus, the sy nthesis and distribution of endothelin-1 (ET-1) and endothelin-3 (ET-3 ) were studied in the retinas of diabetic and nondiabetic animals. Met hods. Levels of ET-1 and ET-3 were determined by radioimmunoassay in o cular tissues of normal rats, and in rats with streptozotocin-induced diabetes of 6 and 12 weeks' duration, insulin-treated and untreated. I n a separate cohort of similarly treated animals, retinal vascular try psin digest preparations were immunostained, using antibodies raised a gainst ET-1 and ET-3. Results. Ocular ET-1 levels were elevated twofol d in diabetic animals that received insulin treatment for 7 days when compared with levels in normal rats. Insulin treatment for 10 days bef ore death caused a fourfold elevation of ET-1 in ocular tissues. Endot helin-1 was also increased in 12-week-old diabetic animals and in thos e maintained on insulin throughout their period of diabetes. Immunoflu orescence to anti-ET-1 within the capillary bed and veins of the retin a in diabetic insulin-treated animals was elevated when compared with digests from normal litter-matched control animals. Ocular tissue ET-3 levels were unaffected by diabetes. Conclusions. Overall ocular and r etinal tissue levels of ET-1 were selectively elevated by diabetes and insulin treatment, suggesting that the endothelins may be involved in the pathogenesis of diabetic retinal microangiopathy.