ACE1/ACE2平衡在氧诱导视网膜病变中的区域性分布及作用机制研究

Investigations on the mechanisms of retinal vascular diseases have been the focus of scientific research. Recent study showed that central retinal artery and vein system was highly evolutional and highly decentralized, and retinal vascular diseases have the characteristics of individual domains. Our early study showed that reaction of different segment of retinal vasculature were different upon the angiotensin II, but distribution of angiotensin receptors was found the same, suggesting that angiotensin converting enzymes (ACE1 and ACE2) which modulated the angiotensin II may be one of the main players in the pathophysiological mechanisms in different segment of retinal vasculature. This study plans to use rat animal model of oxygen-induced retinopathy, to investigate the balance of ACE1 and ACE2 in different areas of retina (distribution of ACE1 and ACE2 and related factors, associated inflammatory factors, and retinal vascular permeability, and signal factors). Furthermore, this study intends to modulate expression of ACE1 or ACE2 via adeno-associated virus, to estimate related retinal structural and functional changes. In summary, this study tries to illuminate the balance of ACE1 and ACE2 in the mechanisms of retinal vascular development and retinal vascular diseases, and to provide new strategy on the treatment of retinal vascular diseases.

视网膜血管性疾病的病理生理机制是目前研究的难点。对视网膜血管的研究提示，视网膜中央动静脉具有高度进化和自主调控的特点，并且视网膜血管性疾病的发生发展具有区域化特点。申请人前期的研究发现视网膜血管的不同节段对血管紧张素II的刺激反应明显不同，但是血管紧张素II受体分布差异不明显，提示调控血管紧张素生成和降解的血管紧张素转化酶（ACE1和ACE2）可能是参与视网膜血管不同节段生理病理机制的关键靶点。本研究拟采用氧诱导的视网膜病变大鼠模型，以ACE1和ACE2的平衡关系为切入点，采用三种分区方法观察视网膜不同区域ACE1和ACE2及其相关因子的表达差异、相应炎性因子的差异、血管通透性的差异；并探求调控ACE1或者ACE2以后，相关信号通路的变化，阐明ACE1和ACE2在视网膜血管发育以及视网膜血管性疾病中的机制，为视网膜血管性疾病的治疗提供新的思路。