Effect of (-)MR-22, a Novel Sigma-1 Receptor Ligant, Against Ischemia/Reperfusion Damage in Rat Retina

Abstract

Abstract: : Purpose: To investigate the effects of (-)MR-22, a novel σ1 receptor ligand, on retinal degeneration using a rat model of ischemia/reperfusion injury. The effects were compared with PRE-084 a well known σ1 agonist. Methods: Sprague-Dawley rats were used. The animals were anaesthetized and the left eye was cannulated with a 27 gauge infusion needle connected to a raised saline reservoir. Retinal ischemia was induced by elevating the intraocular pressure to 120 mmHg for 45 min. Measurement of IOP was made by a Tono-Pen XL tonometer. (-)MR-22 or PRE-084 were injected i.p. (1 mg/kg; in a volume of 1ml/kg) at 5 min prior to the start of retinal ischemia and immediately after reperfusion. The eyes were enucleated 3 days or 7 days after ischemia insult for the biochemical assays (glucose and lactate) and the histopathologic study respectively. Results: (-)MR-22 prevents ischemia-induced damage to the inner retina. The percentage survival of retinal ganglion cells (RGCs) in the (-)MR-22-treated group (80.3±10.7%) was statistical different (p<0.01) compared to the saline/ischemic group (49.2±6.4%). PRE-084 prevented the ischemia-induced loss of RGCs (57.8±7.6%) compared to the saline/ischemia group but the difference was not statistically significant. Retinal biochemical changes as increase of lactate content and decrease of glucose were statistical inhibited (p<0.01) only in the (-)MR-22-treated group compared to the saline/ischemic group. The lack of effect for PRE-084 could be due to a rapid degradation of molecule. Conclusion: The data demonstrate that (-)MR-22 serves as neuroprotective agent and attenuates the ischemic retinal injury induced by raising the IOP. These observations may be of major importance in view of the therapeutic use of selective σ1 agonist in retinal diseases and various types of glaucoma. CR:N

Keywords: 489 neuroprotection • 448 ischemia