En. Su et al., ALTERED VASOACTIVITY IN THE EARLY DIABETIC EYE - MEASURED IN THE ISOLATED-PERFUSED RAT EYE, Experimental Eye Research, 61(6), 1995, pp. 699-711
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