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Fangfang Qiu, Younghwa Shin, Danyang Chen, Guotao Deng, Jian-Xing (Jay) Ma; Therapeutic Potential of Monoclonal Antibodies Blocking the Wnt Pathway in Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4513.
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© ARVO (1962-2015); The Authors (2016-present)
We demonstrated previously that Mab2F1, a monoclonal antibody blocking the Wnt pathway, has therapeutic potential for diabetic retinopathy and choroidal neovascularization (NV). The purpose of this study was to evaluate if Mab2F1 and its humanized antibody, H1L1, have inhibitory effects on corneal NV and investigate the underlying mechanism.
Corneal NV was induced by alkali burn in anesthetized rats which were then subconjunctivally injected with 50µg/50µl of Mab2F1 or H1L1, with nonspecific mouse IgG or human IgG as control, respectively (n=10 per group) on days 0, 2 and 4 after alkali burn. Corneal NV and inflammation were evaluated using quantification of area of corneal NV and inflammatory index by slit lamp on days 2, 4, 6 and 8 after akali burn. Corneal levels of CD31, pro-angiogenic and pro-inflammatory factors, were measured by immunostaining and Western blot on day 8 after alkali burn. The effect of Mab2F1 or H1L1 on expression of Wnt pathway components in corneal NV was determined by Western blot analysis and immunostaining. The anti-angiogenic effect of Mab2F1 in vitro was assessed using human umbilical vein endothelial cells (HUVECs) stimulated by Wnt3a conditional medium (WCM). The effect of Mab2F1 on Wnt signaling induced by WCM was examined in human corneal epithelial (HCE) cells by luciferase assay and Western blotting. Two-tailed Student’s t-test was used for statistical analysis.
Areas of corneal NV and inflammatory index, levels of CD31, pro-angiogenic and pro-inflammatory factors were all significantly reduced in the Mab2F1 and H1L1-treated groups, compared with that in control IgG-treated groups on days 4, 6 and 8 after alkali burn (all p<0.01). Mab2F1 and H1L1 displayed similar effects on NV and inflammation (all p>0.05). Mab2F1 and H1L1 significantly suppressed Wnt signaling in the cornea with NV. Mab2F1 significantly inhibited proliferation, migration and tube formation of HUVECs in a dose-dependent manner. Mab2F1 displayed robust inhibition of Wnt signaling and downregulated the expression of pro-angiogenic and pro-inflammatory factors induced by WCM in HCE cells in a dose-dependent manner.
Mab2F1 and H1L1 are effective on inhibiting corneal NV and inflammation via blocking Wnt signaling, suggesting therapeutic potential for corneal NV.
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