Purchase this article with an account.
Hu Huang, Stanley A. Vinores; Involvement Of Both VEGFR1 And R2 In Retinal Neovascularization (NV) And Vascular Permeability. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4002.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
VEGFR1 and 2 signaling have both been increasingly shown to mediate adverse complications of ischemic retinopathies, including retinopathy of prematurity, wet age-related macular degeneration, and diabetic retinopathy (DR). The purpose of this study is to demonstrate and compare the roles of VEGFR1 and 2 on ocular NV and vascular leakage.
The oxygen-induced ischemic retinopathy (OIR) model was used to generate retinal NV in neonatal mice by exposing them to 75% O2 at P7 for 5 days and then returning them to room air for 5 days. Neutralizing antibodies to VEGFR1 (MF1;Lilly/ImClone) and VEGFR2 (DC101; Lilly/ImClone) were injected intraperitoneally at P12 and P15. Evaluation of retinal NV was performed at P17 following staining of retinal flat-mounts with anti-mouse PECAM-1 or griffonia simplicifolia isolectin-B4 conjugated to Alexa Fluor 594. The blood-retinal barrier (BRB) was also assessed at P17 using 3H-mannitol as a tracer. Mice were made diabetic with streptozotocin.
With the OIR model, MF1 significantly inhibited hypoxia-induced retinal NV within the dosage range of 6.25-100mg/kg body weight. Both MF1 and DC101 significantly suppressed retinal NV: DC101 suppressed retinal NV by 45% (p=0.013) and MF1 suppressed retinal NV by 50% (p<0.0002) at the 25mg/kg dosage. MF1 was even more effective at inhibiting BRB breakdown than DC101 (MF1:73% inhibition, p=0.001; DC101:12% inhibition, p=0.003). Antibody to the VEGFR1 ligand, PlGF (Roche/Thrombogenics) did not inhibit BRB breakdown in this model. Immunofluorescence staining shows that expression of both VEGFR1 and 2 is increased in retinas of diabetic mice, particularly in retinal vessels, suggesting that anti-VEGFR1 may also be beneficial in treating DR.
Our study provides further evidence that both VEGFR1 and VEGFR2 signaling mediate the adverse complications of ischemic retinopathies, and suggests that MF1 and DC101 are potential therapeutic agents for ischemic retinopathies.
This PDF is available to Subscribers Only