Topical Nipradilol Exerts a Neuroprotective Ability in Experimental Rat Retina Through Nitric Oxide Donation

Abstract

Abstract: : Purpose: We have reported that nipradilol(NP), α1– and ß– adorenoreceptaor–blocker. inhibited apoptosis in retinal neurons in culture by a nitric oxide (NO) donative action (ARVO 2004,914). The purpose of this study is to see if topical NP instillation could inhibit apoptosis of in vivo retinal neurons in diabetic rats. Methods: Male Sprague–Dawley rats were induced diabetes by tail–vein injection of streptozotocin (STZ). One– or three– month STZ–diabetic and age–matched control rats received 10µl of eye drops either of 0.25%NP, vehicle, or desnitro–NP in the right eyes twice daily for 5 days. The left eyes were untreated. Intraocular pressure (IOP) was measured with Tonopen^®. The retinas were dissected, flat–mounted, and subjected to terminal dUTP nick end labeling (TUNEL) staining. TUNEL positive cells per unit area of whole retina were counted and compared with ANOVA. Results: IOP after NP instillation was not different among treated and untreated eyes both in one– and three–month diabetic rat (p=0.45, P=0.20). TUNEL positive cells per 0.5cm² retina were 15.8±3.9, 40.9±11.9, 22.8±9.5 in control retinas (n=5), one–month diabetic retinas with vehicle (n=6), and those with NP instillation (n=5), respectively. The TUNEL positive cell number was significantly smaller in diabetic retina with NP instillation than in those with vehicle (p=0.01), which was not different from controls (p=0.28). The absolute number of TUNEL positive cells in three–month diabetic retinas was similar as in one–month diabetics. The ratio of TUNEL positive cells in the treated, right eyes to the untreated, left eyes was as follows; NP,0.55±0.098 (n=4); vehicle,1.1±0.39 (n=4); desnitro–NP,1.07±0.29 (n=4), respectively. The TUNEL positive cell ratio was significantly reduced in diabetic retinas with NP instillation than in those with vehicle (p=0.023) and desnitro–NP instillation (p=0.031). Conclusions: Topical instillation of NO inhibits apoptosis of neurons and/or glial cells through NO donation in experimental diabetic rat retina.

Keywords: apoptosis/cell death • neuroprotection • nitric oxide