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Fangfang Qiu, Younghwa Shin, Danyang Chen, GUOTAO DENG, Jian-Xing (Jay) Ma; Inhibitory Effects of Monoclonial Antibodies Blocking the Wnt Pathway on Experimental Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5021.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous studies demonstrated that Mab2F1, a murine monoclonal antibody blocking the Wnt pathway, has therapeutic potential for diabetic retinopathy and choroidal neovascularization (NV). Our present study evaluated whether Mab2F1 and its humanized antibody, H1L1, have inhibitory effects on corneal NV and investigated the underlying mechanism.
Corneal NV was induced by alkali-burn in anesthetized rats, which were then treated with subconjunctival injection of 50 µg/eye of Mab2F1 or H1L1 every other day for 8 days, with nonspecific mouse- or human-IgG as control, respectively (n=6/group). Corneal NV and inflammation were evaluated by slit lamp and histological examination. Expression of pro-angiogenic and pro-inflammatory factors, and activity of Wnt signaling pathway in both in vivo and in vitro models were examined by immunostaining, Western blotting and luciferase-based promoter assay. The possible toxicities of Mab2F1 and H1L1 were estimated in vitro by MTT assay. Data were analyzed with independent-samples t-test.
Compared with control groups, Mab2F1 and H1L1 significantly reduced the NV areas and inflammatory index in animal model, downregulated the expression of pro-angiogenic and pro-inflammatory factors including VEGF, ICAM-1 and TNF-α, and components of Wnt signaling pathway such as LRP6, p-LRP6 and Non-p-β-catenin in the cornea with NV and in human corneal epithelial (HCE) cells induced by Wnt3a conditional medium (WCM) (all p<0.01). Mab2F1 and H1L1 also inhibited β-catenin transcriptional activity induced by WCM in HCE cells. No toxic effects were observed in quiescent HCE.
Mab2F1 and H1L1 have therapeutic potential for corneal inflammation and NV via blocking Wnt signaling.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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