Experimental evidence for the topical use of angiotensin-converting enzyme inhibitors in eye drops for eye ischemia treatment

Abstract

Purpose: to evaluate the topical use effect of angiotensin-converting enzyme (ACE) inhibitor (iACE) Enalaprilat in eye drops on eye blood flow volume, hypoxia degree, ACE activity, and total antioxidant activity (TAA) in aqueous humor of rabbits with experimental ocular ischemia.Material and methods. Transient ocular ischemia in 30 Chinchilla rabbits was induced by subconjunctivally injecting 0.2 ml of 1 % Phenylephrine. Ocular ischemia degree was assessed by the minute volume of blood flow (MBF), determined with the help of ophthalmic plethysmography. 0.125 % Enalaprilat was administered by instillations. A CE activity in aqueous humor was measured using a spectrofluorometric assay with 0.1 mM Z-Phe-His-Leu substrate; the degree of hypoxia was estimated by the level of lactate in aqueous humor, which was determined by the enzymatic amperometric method. TAA was determined by registering chemiluminescence kinetics in the hemoglobin-H2O2-luminol model system.Results. A single instillation of iACE in the intact rabbit eye caused a decline of MBF value and A CE activity in aqueous humor. In ocular ischemia, ACE activity and t he lactate level in aqueous humor are increasing, while TAA is decreasing. Enalaprilat instillation in the eyes with ischemia lead to the normalization of MBF, ACE activity, lactate level and TAA in aqueous humor.Conclusion. Topical iACE in eye drops can penetrate eye tissues. Instillations of iACE during ischemia cause a remarkable increase of eye blood flow and reduce ACE activity, which is increased in ischemia. The anti-ischemic effect of iACE is accompanied by antihypoxant and antioxidant effects. Thus, iACE in eye drops can be used in ophthalmology as an anti-ischemic agent.