(Pro)renin Receptor: A Treatment Target for Diabetic Retinopathy?

  1. Jennifer L. Wilkinson-Berka1 and
  2. Duncan J. Campbell2
  1. 1Department of Immunology, Monash University, Prahran, Victoria, Australia;
  2. 2St. Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
  1. Corresponding author: Jennifer L. Wilkinson-Berka, jennifer.wilkinson-berka{at}med.monash.edu.au.

Many lines of evidence implicate the renin-angiotensin system in the pathogenesis of diabetic retinopathy. A recent multicenter trial showed that angiotensin II type 1 (AT1) receptor blockade (ARB) reduced the incidence of retinopathy in type 1 diabetic patients and improved the regression of retinal disease in type 2 diabetic patients (1,2). However, the failure of ARB to prevent progression of diabetic retinopathy indicates a role for mechanisms additional to angiotensin II in its pathogenesis. In this issue of Diabetes, Satofuka et al. (3) provide evidence that prorenin and the (pro)renin receptor, acting in part through mechanisms unrelated to angiotensin II, may contribute to the pathogenesis of diabetic retinopathy. This evidence holds promise for new therapies for diabetic retinopathy and other complications of diabetes.

Prorenin is a high–molecular weight biosynthetic precursor of renin. It has a low intrinsic activity of <2% of the activity of renin (4) because it has an amino-terminal 43–amino acid prosegment that masks the active site, thereby preventing access by the renin substrate—angiotensinogen. Renal juxtaglomerular cells are the only known site of renin production, whereas the kidney and a number of extrarenal tissues including adrenal, ovary, testis, placenta, and retina produce prorenin (57). Plasma prorenin concentrations are ∼10- to 20-fold higher than those of renin (4). Prorenin concentrations in plasma and vitreous fluid are increased in diabetic subjects (6,8), and plasma prorenin is a powerful marker for both prevalent and incident microvascular complications of diabetes, including nephropathy, retinopathy, and …

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