A Role for Endothelin in the Development of Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy?

Abstract

Abstract: : Purpose: An early subnormal retinovascular oxygen supply regulation (ΔPO₂) in diabetic rats is a good predictor of the risk of development of retinopathy and is useful for assessing therapeutic efficacy, but the biochemical mechanisms underlying the development of a subnormal ΔPO₂ are not known. In this study, we evaluated the role of the potent vasoconstrictor endothelin in regulating ΔPO₂ in control and diabetic rats. Methods: In controls rats, either vehicle (Vech., n = 7) or 10^–6 M endothelin–1 (ET–1, n = 5) were injected intravitreally over the optic nerve head; retinal ΔPO₂ during a 2 min carbogen challenge was measured 30 min later. In a separate set of experiments, three rat groups were maintained for 3 mo: normoglycemic (n = 7), diabetic (n = 9), or diabetic fed bosentan (a well–tolerated and dual ETA/ETB receptor antagonist, 100 mg/kg/day in the chow, n = 5); retinal ΔPO₂ measurements were obtained during a 2 min carbogen challenge. Results: In control rats, retinal ΔPO₂ within 2.5 mm from optic nerve head was subnormal (P < 0.05) following ET–1 injection, compared with Vech. injected eyes. In both untreated diabetic rats and in bosentan treated rats, superior hemiretinal ΔPO₂ was subnormal (P < 0.05) while inferior hemiretinal ΔPO₂ remained normal (P > 0.05), compared with controls. Conclusions: In control rats, elevated vitreal endothelin levels alone can produce a subnormal retinal oxygenation response to a carbogen inhalation challenge. However, in diabetic rats, we find no evidence for an association between the reported increase in ET activity and the development of a subnormal retinal ΔPO₂.

Keywords: diabetes • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • retina