Prorenin and the (pro)renin receptor: recent advances and implications for retinal development and disease

Purpose of review 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. Recent findings 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. Summary 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.