VEGF TrapR1R2 Suspended in the Semifluorinated Alkane F6H8 Inhibits Inflammatory Corneal Hem- and Lymphangiogenesis.

Viet Nhat Hung Le, Deniz Hos, Yanhong Hou, Madlen Witt, Mikhail Barkovskiy, Felix Bock, Claus Cursiefen

Translational vision science & technology 2020 Oct

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Semifluorinated alkanes (SFAs) are used at the ocular surface as lubricants or vehicles for drugs. The purpose of this study was to test the effect of vascular endothelial growth factor (VEGF) TrapR1R2 suspended in the SFA perfluorohexyloctane (Trap/F6H8) on corneal neovascularization. Suture placement was used to induce inflammatory corneal neovascularization in mice. Treatment groups were: Trap/F6H8, VEGF TrapR1R2 as aqueous formulation dissolved in phosphate buffer (Trap), F6H8, and phosphate buffer (controls). Eye drops were applied 3×/daily for 2 weeks. Afterward, corneas were stained with CD31 and LYVE-1 to analyze corneal hem- and lymphangiogenesis. To investigate the effect of on inflammatory cell recruitment, corneal CD45+ cells were quantified. In addition, epithelial wound closure after debridement was assessed by corneal fluorescein staining. Trap/F6H8 was as effective as Trap in inhibiting corneal hemangiogenesis and lymphangiogenesis after 2 weeks of treatment. After 3 days of treatment, Trap/F6H8 was even more effective than Trap in inhibiting corneal hemangiogenesis. Both treatment groups (Trap/F6H8 and Trap) significantly reduced corneal CD45+ cell recruitment. Epithelial closure after debridement was unaffected by Trap/F6H8 or Trap. In this study, we demonstrate that F6H8 is a potential carrier for VEGF TrapR1R2 to topically treat corneal neovascularization. Our findings might open new treatment avenues for local anti-angiogenic therapy at the cornea, as F6H8 is already approved for the usage at the ocular surface. With this study we show for the first time that SFAs can serve as carriers for anti-angiogenic drugs at the ocular surface. Copyright 2020 The Authors.

Citation

Viet Nhat Hung Le, Deniz Hos, Yanhong Hou, Madlen Witt, Mikhail Barkovskiy, Felix Bock, Claus Cursiefen. VEGF TrapR1R2 Suspended in the Semifluorinated Alkane F6H8 Inhibits Inflammatory Corneal Hem- and Lymphangiogenesis. Translational vision science & technology. 2020 Oct;9(11):15