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R.L. Roberts, H. Luan, B.A. Berkowitz; A Role for Endothelin in the Development of Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy? . Invest. Ophthalmol. Vis. Sci. 2005;46(13):418.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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