Wilkinson-Berka Jennifer L, Miller Antonia G, Fletcher Erica L
Department of Immunology, Monash University, Melbourne, Victoria, Australia.
Front Biosci (Elite Ed). 2010 Jun 1;2(3):1054-64. doi: 10.2741/e163.
Prorenin, the inactive precursor of renin has been suggested to be an indicator of diabetic complications including retinopathy. This concept was originally based on findings that prorenin is elevated in the plasma and vitreous of patients with diabetic retinopathy. Experimental studies in animal models of diabetic retinopathy and retinopathy of prematurity, have confirmed these reports and localized prorenin to macroglial Muller cells and blood vessels. The identification of a (pro)renin receptor ((P)RR) which binds both prorenin and renin, and influences intracellular signaling pathways independently of angiotensin II, suggests that prorenin-(P)RR may be pathogenic under certain circumstances. Given recent evidence from clinical trials that angiotensin II blockade improves to some extent retinopathy in diabetic patients, the development of (P)RR antagonists could have promise as an adjunct treatment for retinal diseases where prorenin is up-regulated. This review will discuss the cellular location of the renin-angiotensin system in the retina, evidence that angiotensin II blockade is beneficial for both retinal vascular, neuronal and glial pathology and place this information in the context of the development of (P)RR inhibitors.
肾素原是肾素的无活性前体，已被认为是包括视网膜病变在内的糖尿病并发症的一个指标。这一概念最初基于糖尿病视网膜病变患者血浆和玻璃体液中肾素原升高的研究结果。糖尿病视网膜病变和早产儿视网膜病变动物模型的实验研究证实了这些报道，并将肾素原定位到神经胶质Müller细胞和血管。一种既能结合肾素原又能结合肾素，并独立于血管紧张素II影响细胞内信号通路的（前）肾素受体（(P)RR）的发现表明，在某些情况下肾素原-(P)RR可能具有致病性。鉴于最近临床试验的证据表明血管紧张素II阻断在一定程度上改善了糖尿病患者的视网膜病变，(P)RR拮抗剂的开发有望成为肾素原上调的视网膜疾病的辅助治疗方法。本综述将讨论视网膜中肾素-血管紧张素系统的细胞定位，血管紧张素II阻断对视网膜血管、神经元和神经胶质病变均有益的证据，并将这些信息置于(P)RR抑制剂开发的背景下。
