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E. Cheung, I. B. Lobov, G. D. Yancopoulos, J. Cao, S. J. Wiegand; Placental Growth Factor (PlGF) Inhibition Decreases Neovascularization and Accelerates Retinal Revascularization in the Murine Model of Oxygen Induced Ischemic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4486.
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In the Vascular Endothelial Growth Factor (VEGF) family, Placental Growth Factor (PlGF) contributes to driven pathological angiogenesis through its affinity to and activation of VEGF Receptor 1 (Flt-1). PlGF is also linked to leukocyte infiltration, and tumor growth, as well as ischemia and wound healing. [Luttun et al., Nature Med. 2002, 8:831-840]. Previously, we have reported that the genetic deletion of PlGF decreased vasoobliteration and pathological neovascularization caused by Induced Retinopathy (OIR) [IOVS 2009 2943: E-462]. In the present studies, we used an anti(α)-PlGF antibody to evaluate the effects of PlGF inhibition in the murine model of OIR, after vessel loss was complete.
Mice were placed in a hyperoxic environment (75% O2) at P6 and returned to room air at P11. The left eyes were injected intravitreally with anti-mouse PlGF-2 Polyclonal Ab (R&D systems) and the right eyes with Fc (control) at P11 and at P14 (Study 1) or at only P14 (Study 2). Retinas were collected at P17 (Study 1) or P16 (Study 2) and flatmounts were stained with FITC-labeled Griffornia simplicifolia lectin I (Vector Laboratories).
The inhibition of PlGF with two intravitreal injections of α-PlGF on days P11 and P14 resulted in a dramatic decrease in the development of pathological neovascularization, while increasing in the rate of normal revascularizations compared to controls. A single injection on day P14 was almost as effective in decreasing vascular abnormalities and the residual avascular area.
This study demonstrates that pharmacological inhibition of PlGF improves blood vessel regrowth and ameliorates vascular abnormalities. These results are consistent with observations in our previous study, which showed that constitutive genetic deletion of PlGF reduces vasoobliteration and pathological angiogenesis.
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