Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy

上皮膜蛋白 2 (EMP2) 阻断可减轻小鼠氧诱导视网膜病变中的病理性新生血管形成

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作者:Brian Aguirre, Meng-Chin Lin, Eduardo Araujo, Cheng-Hsiang Lu, David Casero, Michel Sun, Steven Nusinowitz, Justin Hanson, Kara Calkins, Lynn Gordon, Madhuri Wadehra, Alison Chu

Conclusions

Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

Methods

Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed.

Purpose

Retinopathy of prematurity (ROP)

Results

Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

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