Prorenin and the (Pro)renin Receptor in Retinal Pathology

Blockade of angiotensin II (Ang II) has potential therapeutic benefit for ocular diseases including diabetic retinopathy and retinopathy of prematurity. Perhaps the most studied is diabetic retinopathy where angiotensin converting enzyme inhibition and angiotensin type 1 receptor blockade (AT1-RB) is beneficial. The importance of Ang II has recently been highlighted with DIRECT (DIabetic REtinopathy Candesartan Trial) reporting that the AT1-RB, candesartan, reduced the incidence of retinopathy in type 1 diabetic patients and enhanced regression in type 2 diabetic patients. Prorenin may also be a causative factor in diabetic retinopathy in humans, with early studies reporting that prorenin is elevated in both plasma and vitreous. Recently, interest in prorenin has re-emerged with the identification of a prorenin receptor [(P)RR] which binds both renin and prorenin and induces signal transduction pathways that are independent of Ang II. Studies by one group have reported that a particular (P)RR inhibitor provides protective effects in experimental retinopathy of prematurity and uveitis. However, controversy exists about the effectiveness of this (P)RR inhibitor with other groups failing to find organ protection. This review discusses these findings and evaluates whether prorenin and the (P)RR may be relevant for certain ocular diseases and a possible target for therapeutic intervention.