Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Australia.
Curr Opin Nephrol Hypertens. 2011 Jan;20(1):69-76. doi: 10.1097/MNH.0b013e328341328a.
The renin-angiotensin system (RAS) is a treatment target for diabetic retinopathy and possibly other ocular diseases. However, angiotensin II blockade, though beneficial in diabetic retinopathy, is not completely retinoprotective. There is speculation that this shortfall is due to incomplete suppression of other RAS components. This review discusses the possibility that prorenin, which initiates the RAS, and the (pro)renin receptor [(P)RR] are potential candidates.
Despite prorenin being elevated in diabetic retinopathy, it remains unclear whether it exerts any functional effects in tissues, including the eye. Of interest are newly identified functions for the (P)RR based on its homology with an accessory protein of vacuolar ATPase, ATP6AP2. These include roles in the viability of the central nervous system, including the retina, via the Wnt signaling pathway. Additionally, (P)RR/ATP6AP2 is implicated in other vacuolar ATPase-related events, including the regulation of cellular pH in the kidney and cell survival. Yet to be determined is whether the effects of (P)RR/ATP6AP2 are relevant to retinal cell function in health and disease and require the participation of its ligand prorenin.
New functions for the (P)RR highlight previously unrecognized roles for this receptor in cellular events that may have implications for both the developing and diseased retina.
肾素-血管紧张素系统（RAS）是糖尿病性视网膜病变和其他可能的眼部疾病的治疗靶点。然而，尽管血管紧张素 II 阻断在糖尿病性视网膜病变中是有益的，但它并不是完全的视网膜保护作用。有人推测，这种缺陷是由于其他 RAS 成分的抑制不完全所致。这篇综述讨论了这样一种可能性，即起始 RAS 的血管紧张素原和（前）血管紧张素受体[（P）RR]可能是潜在的候选药物。
尽管在糖尿病性视网膜病变中血管紧张素原升高，但它是否在组织中（包括眼睛）发挥任何功能作用仍不清楚。有趣的是，（P）RR 基于其与液泡 ATP 酶辅助蛋白 ATP6AP2 的同源性，具有新的功能。这些功能包括通过 Wnt 信号通路影响中枢神经系统（包括视网膜）的存活。此外，（P）RR/ATP6AP2 还与其他液泡 ATP 酶相关事件有关，包括调节肾脏中的细胞 pH 值和细胞存活。目前尚不清楚（P）RR/ATP6AP2 的作用是否与健康和疾病状态下的视网膜细胞功能有关，以及是否需要其配体血管紧张素原的参与。
（P）RR 的新功能突出了该受体在细胞事件中的先前未被认识到的作用，这些作用可能对发育中和患病的视网膜都有影响。
