ALTERED VASOACTIVITY IN THE EARLY DIABETIC EYE - MEASURED IN THE ISOLATED-PERFUSED RAT EYE

The effect of 4 weeks streptozotocin-induced diabetes on ocular vascul ar resistance responses to noradrenalin (NA), adrenalin (A), phenyleph rine (PHE), isoproterenol (ISOP), prostaglandin F-2 alpha(PGF(2 alpha) ). 5-hydroxytryptamine (5-HT) and angiotensin II (ANG II), was determi ned using a newly-developed, isolated, arterially-perfused rat eye pre paration, by comparing responses from control and diabetic eyes. After extensive preliminary experiments to establish optimum parameters, th e ophthalmic artery of enucleated control and diabetic rat eyes was ca nnulated and the retinal and uveal vasculature perfused at a constant now with Na+-Krebs solution after streptozotocin-induced diabetes had been established for 4 weeks. The eyes were maintained in an environme nt-controlled organ bath. Perfusion pressure was monitored as increasi ng log M concentrations of agonists were added to the perfusate. Total ocular resistance could be calculated from knowledge of now and press ure. In control eyes, NA, A, PHE, PGF(2 alpha), and 5-HT all produced dose-dependent increases in total vascular resistance, with the follow ing order of potency: NA = A > 5-HT > PHE = PGF(2 alpha) at 10(-4) M. The ocular circulation was not sensitive to isoproterenol and angioten sin II. In diabetic eyes responses to NA, A, PGF(2 alpha) and 5-HT wer e altered. Diabetic responses to NA and A had lower thresholds with la rger resistance increases at low concentrations. However, the rate of increase in resistance with concentration was more gradual in diabetic eyes so that at 10-(4) M control responses were larger. Diabetic resi stance responses to PGF(2 alpha), had the same threshold as in control eyes, but were greater in magnitude with an earlier peak at 10(-4) M. In contrast diabetic resistance responses to 5-HT were reduced, peake d at a lower resistance at 10(-4) M, but had the same threshold as tho se in the control eye. Basal vascular resistances in control: 3.14 +/- 0.32 mmHg min mu l(-1) (n = 28), and diabetic eyes: 3.44 +/- 0.19, mm Hg min mu l(-1) (n = 36), were not significantly different. Vasoactivi ty in the early diabetic eye is disturbed with the effective balance b etween different agonists altered in favour of catecholamines at physi ological concentrations. This may be related to the early changes in b lood now and oxygen distribution already reported in the rat eye, as w ell as changes to autonomic function. The isolated perfused rat eye is a valuable technique for investigating such vascular reactivity in an imal models of retinal disease. (C) 1995 Academic Press Limited