Abstract
Purpose: :
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 for diabetic retinopathy (DR). The goal of this study is to elucidate (pro)renin receptor [(P)RR]-associated pathogenesis of fibrovascular proliferation in DR.
Methods: :
Total thirty-nine vitreous samples from patients with proliferative DR (PDR) and non-DR were collected and protein levels of soluble (P)RR [s(P)RR] were measured by ELISA. Double staining immunohistochemistry was performed to assess localization of (P)RR in human fibrovascular tissues from PDR eyes. The vascular density of fibrovascular tissues was evaluated by immunofluorescence for CD34. Vascular endothelial growth factor (VEGF) expression was quantified by real-time PCR in primary normal human retinal microvascular endothelial cells.
Results: :
(P)RR immunoreactivity was detected in vascular endothelial cells, co-localized with prorenin, phosphorylated extracellular signal-regulated kinase and VEGF. The protein level of s(P)RR was increased in the vitreous fluid of patients with PDR, compared to that in non-DR samples. The s(P)RR protein expression in the vitreous was significantly correlated with both vitreous VEGF protein levels and the vascular density of fibrovascular tissues. In vitro administration of prorenin caused significant upregulation of VEGF165 mRNA expression.
Conclusions: :
Our data using clinical samples provide evidence that (P)RR is associated with angiogenic activity in PDR.
Keywords: diabetic retinopathy • vascular endothelial growth factor