Total retinal nitric oxide level is increased under elevated intra-ocular pressure

Abstract

Purpose: Nitric oxide (NO) is a well-known vaso-dilator but its modulation in the retina is unclear. This study was conducted to quantify the total NO level and retinal ganglion cell (RGC) loss in an experimental glaucoma model. Methods: Three quarters of the episcleral drainage vessels (right eyes) of SD rats were thermally blocked using laser irradiation while the left eyes served as controls. We measured the intra-ocular pressure (IOP) using a digital tonometer (TonopenTM) 21 days, 28 days and 35 days after the laser treatment. We also measured total NO levels of the retina and the eyecup using a spectro-photometric assay, and RGC numbers by counting the retro-grade fluoro-gold stained cell bodies for the laser-treated and control eyes after 35 days. Results: The laser treatment significantly increased the IOP by approximately two-folds throughout the whole period of measurements (p<0.0001). The mean total RGC number decreased significantly from 98 7255383 (SEM) to 69 2765592 (p=0.008), or 29.8% reduction, in the laser-treated eyes after 35 days. The mean total NO level in the laser-treated retina was significantly increased by 2.4x compared with controls (p=0.016), but no significant difference was found in the eyecups (p≷0.05). Conclusion: Laser treatment resulted in significant IOP elevation and RGC loss, suggesting that thermal coagulation of drainage vessels provides an alternate model for glaucoma study. Retinal NO level is increased by about 2 times on Day 35 post-laser treatment. Since NO is capable of producing powerful peroxynitrite anion and hydroxyl radical, increasing NO production has a potential oxidative role for RGC loss in glaucoma.