Endogenous Cgrp In The Role Of Stress-induced Apoptosis Of Retinal Cells And Sensory Factors

Background: The stress induced by coronary artery occlusion could provoke a significant increase in apoptosis of rat retinal cells, ensory nerves are involved in the modulation of apoptotic injury of retina. Meantime, coronary artery occlusion could induce increasing expression of calcitonin gene related peptide (CGRP) in retina. In what way ensory nerves madulate apoptotic injury of retina need a further study.Object: The aim of the study was to investigate the role of CGRP in the pathology of stress-induced apoptosis of the retina cells and the role of sensory nerve in the expression of calcitonin gene-related peptide (CGRP)in retina during coronary artery occlusion. Methods: (1) The acute myocardial ischemia model was established by ligating the left anterior descending branch of coronary artery in 12 male Sprague-Dawley rats. The rats were randomized into CGRP_8-37 injection group and normal saline injection group, 6 rats 12 eyes for every group. CGRP_8-37 (10^-7mol/L), a specific antagonist of CGRP receptor, was intravenously injected in CGRP_8-37 group by caudal vine at 15 minutes prior to the CAO, and the equivalent amount of normal saline was used at the same fashion in normal saline group. The retinal samples of the rats were collected at 3 hours after CAO for TUNEL staining and caspase-3 activity detection respectively. (2)Twelve 48h male Sprague-Dawley rats was divided into two groups. One was capsaicin denervated goup, another was control group. When they grow up to 250-300g, the acute myocardial ischemia model was established by ligating the left anterior descending branch of coronary artery for 3 hours. The animals were divided into denervation CAO3h group and normal CAO3h group. The samples of the retina were collected at 3 hours of CAO for EIA to measure the CGRP in the retina under the impact of acute stress retina.Results: (1) The cellular displacement was observed in inner and outer nuclear layer, and vacuolar degeneration of retinal ganglion cells was found in the CAO animals. The total apoptosis index of retinal cells in CGRP_8-37 group was significantly higher than that in normal saline group (42.8%±2.8% vs 37.5%±2.9%, t=-3.244, P<0.01). The retinal capase-3 activity was significantly enhanced in the CGRP_8-37 group compared with saline group(11.3±3.1 fold vs 4.9±1.2 fold, t=-4.603, P<0.01) at 3 hours of CAO.(2)The concentration of CGRP was 17.2±3.3 pg/ml in the denervation CAO3h group while the CGRP was 29.4±9.0 pg/ml in the normal group. The difference of the expression of CGRP was statistically significant (P<0.05).Conclusion: (1) The results suggest that the endogenous CGRP may play an anti-apoptotic role in the stress-induced retinal cell injury. (2)The stress induced by coronary artery occlusion could provoke a significant reduction of CGRP in the retinal cells of the rats with denervation of capsaicin sensitive sensory afferent nerves. Sensory nerve play an key modulation role in the process of retina CGRP expression evoked by acute stress.