Prorenin and the (pro)renin receptor: do they have a pathogenic role in the retina?

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.