Receptor-associated prorenin system contributes to development of inflammation and angiogenesis in proliferative diabetic retinopathy.

Atsuhiro Kanda,Susumu Ishida

doi:10.1186/s41232-016-0027-0

Abstract

The renin-angiotensin system (RAS) plays a potential role in the development of end-organ damage, and tissue RAS activation has been suggested as a risk factor of several diseases including diabetes. So far, using animal disease models, we have shown molecular mechanisms, in which tissue RAS stimulates retinal angiogenesis, and the critical roles of (pro)renin receptor [(P)RR] in retinal RAS activation and its concurrent intracellular signal transduction, referred to as the receptor-associated prorenin system (RAPS). Moreover, we recently reported that the protein levels of prorenin and soluble (P)RR increased in the vitreous fluids obtained from patients with proliferative diabetic retinopathy (PDR), suggesting the association of (P)RR with vascular endothelial growth factor (VEGF)-driven angiogenic activity in human PDR, and also showed a close relationship between the vitreous renin activity and VEGF-induced pathogenesis of diabetic retinopathy. Our data using animal disease models and human clinical samples suggest that both vitreous RAS and retinal RAPS play critical roles in the molecular pathogenesis of diabetic retinopathy.

Highlights

Diabetic retinopathy (DR) is one of the severe complications of diabetes and leading cause of severe vision loss and blindness when it progresses to the stage of proliferative DR (PDR) characterized by fibrovascular proliferation
We previously revealed a significant contribution of VEGF165 isoform to angiogenic activity in PDR, showing that fibrovascular tissues co-expressing vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 and neuropilin (NRP) 1, the specific receptor for VEGF165, were highly vascularized [5,6,7]
We focus on the relationship between diabetic retinopathy and tissue renin-angiotensin system (RAS) and suggest a novel concept for the molecular pathogenesis of tissue RAS in the vitreous, referred to as “vitreous RAS.”

Summary

Introduction

Diabetic retinopathy (DR) is one of the severe complications of diabetes and leading cause of severe vision loss and blindness when it progresses to the stage of proliferative DR (PDR) characterized by fibrovascular proliferation. Vitreous renin-angiotensin system and retinal receptor-associated prorenin system in diabetic retinopathy Several types of organ damage are known to result from activation of tissue RAS.

Results

Conclusion