Role of prorenin in the pathogenesis of retinal neovascularization.

PURPOSE: To determine the role of prorenin in the pathogenesis of retinal neovascularization, we evaluated the inhibitory effect of the handle region peptide (HRP) on retinal neovascularization.

METHODS

Neonatal C57BL6 mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and placed in room air. The animals received HRP (1.0 or 0.1 mg/kg/day), captopril (10 mg/kg/day), or normal saline from P12 to P17. Following enucleation of the eyes, the retina was dissected for whole-mount retinal sections and semiquantitative analysis of mRNA of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), fms-like tyrosine kinase 1 (Flt-1), fetal liver kinase 1 (Flk-1), angiopoietin 2 (Ang2), and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2).

RESULTS

The average numbers of neovascular nuclei in retinopathy of prematurity treated with normal saline, captopril, and HRP (0.1 or 1.0 mg/kg/day) were 37.2+/-8.6, 7.7+/-3.4, 39.5+/-7.3, and 6.5+/-2.7, respectively. HRP (1.0 mg/kg/day) and captopril inhibited neovascularization in rhodamine-perfused retina; HRP (0.1 mg/kg/day) did not. Semiquantitative analysis of mRNA for angiogenic factors showed that HRP (1.0 mg/kg/day) inhibited overexpression of PIGF, Flt-1, and Ang2.

CONCLUSIONS

HRP inhibits retinal neovascularization by interfering with nonproteolytic activation of prorenin, indicating that prorenin may promote retinal neovascularization.