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Crystal Shin, Xiaoyong Yuan, Daniela Marcano, Lucas Isenhart, Ken Simmons, Stephen C Pflugfelder, Ghanashyam Acharya; Anti-Angiogenic Polymer Therapeutic for Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3516.
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© ARVO (1962-2015); The Authors (2016-present)
Currently corneal neovascularization is treated with topical formulations of anti-inflammatory or anti-VEGF drugs which can cause adverse side effects. The purpose of this study was to develop a non-invasive biopolymer therapeutic nanowafer to treat corneal neovascularization. The in vivo efficacy of the nanowafer was evaluated in a murine ocular burn model.
A sulfated polysaccharide, dextran sulfate (DS) nanowafers and an antiangiogenic drug, axitinib, loaded DS nanowafers were fabricated by hydrogel template strategy. The chemical burn induced mouse corneas were treated daily with the DS nanowafers, axitinib loaded DS (Axi-DS) nanowafers, DS eye drops to compare their therapeutic efficacies and to evaluate synergistic effect of DS. After treatments, mouse corneas were subjected to immunofluorescence imaging and RT-PCR analyses.
Overall, the nanowafer treatment minimized corneal neovascularization when compared to untreated ocular burn corneas in murine models. Immunofluorescence images presented CD31 positive vasculature endothelium in corneas and showed the DS nanowafer treatment was as effective as Axi-DS nanowafer treatment in suppressing neovascularization. The RT-PCR analysis revealed that after five days of DS nanowafer treatment, gene expressions of proinflammatory cytokines (IL-1α and IL-1β) and angiogenic factors (VEGFA, VEGFR1, and VEGFR2) were downregulated (Figure 1). This result showed that DS nanowafer had anti-angiogenic effect on inhibiting corneal neovascularization.
This study demonstrated the anti-–angiogenic effect of a biopolymer, dextran sulfate, in a murine ocular burn model. In addition, an anti-angiogenic drug incorporated dextran sulfate nanowafer maximized their therapeutic efficacies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1. RT-PCR analysis showing that downregulation of proinflammatory cytokines and angiogenic factors by nanowafer treatments
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