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VEGF 陷阱悬浮于半氟化烷烃 F6H8 中抑制炎症性角膜血管和淋巴管生成。

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

机构信息

Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany.

Department of Ophthalmology, Hue University of Medicine and Pharmacy, Hue University, Vietnam.

出版信息

Transl Vis Sci Technol. 2020 Oct 14;9(11):15. doi: 10.1167/tvst.9.11.15. eCollection 2020 Oct.

DOI:10.1167/tvst.9.11.15
PMID:33117607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7571278/
Abstract

PURPOSE

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) Trap suspended in the SFA perfluorohexyloctane (Trap/F6H8) on corneal neovascularization.

METHODS

Suture placement was used to induce inflammatory corneal neovascularization in mice. Treatment groups were: Trap/F6H8, VEGF Trap 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.

RESULTS

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.

CONCLUSIONS

In this study, we demonstrate that F6H8 is a potential carrier for VEGF Trap 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.

TRANSLATIONAL RELEVANCE

With this study we show for the first time that SFAs can serve as carriers for anti-angiogenic drugs at the ocular surface.

摘要

目的

半氟化烷烃(SFAs)在眼表面用作润滑剂或药物载体。本研究旨在测试悬浮在全氟己基辛烷(F6H8)中的血管内皮生长因子(VEGF)陷阱(Trap/F6H8)对角膜新生血管形成的影响。

方法

缝线放置用于诱导小鼠炎症性角膜新生血管形成。处理组为:Trap/F6H8、溶解在磷酸盐缓冲液中的 VEGF Trap 水溶液(Trap)、F6H8 和磷酸盐缓冲液(对照)。每日滴眼 3 次,持续 2 周。之后,用 CD31 和 LYVE-1 染色分析角膜血管生成和淋巴管生成。为了研究对炎症细胞募集的影响,定量了角膜 CD45+细胞。此外,通过角膜荧光素染色评估清创后上皮伤口闭合情况。

结果

在治疗 2 周后,Trap/F6H8 与 Trap 一样有效抑制角膜血管生成和淋巴管生成。在治疗 3 天后,Trap/F6H8 在抑制角膜血管生成方面甚至比 Trap 更有效。两种治疗组(Trap/F6H8 和 Trap)均显著减少角膜 CD45+细胞募集。Trap/F6H8 或 Trap 对清创后的上皮闭合无影响。

结论

在这项研究中,我们证明 F6H8 是一种将 VEGF Trap 局部递送至角膜新生血管化的潜在载体。我们的发现可能为角膜局部抗血管生成治疗开辟新的治疗途径,因为 F6H8 已获准用于眼部表面。

翻译后的文本

目的

半氟化烷烃(SFAs)在眼表面用作润滑剂或药物载体。本研究旨在测试悬浮在全氟己基辛烷(F6H8)中的血管内皮生长因子(VEGF)陷阱(Trap/F6H8)对角膜新生血管形成的影响。

方法

缝线放置用于诱导小鼠炎症性角膜新生血管形成。处理组为:Trap/F6H8、溶解在磷酸盐缓冲液中的 VEGF Trap 水溶液(Trap)、F6H8 和磷酸盐缓冲液(对照)。每日滴眼 3 次,持续 2 周。之后,用 CD31 和 LYVE-1 染色分析角膜血管生成和淋巴管生成。为了研究对炎症细胞募集的影响,定量了角膜 CD45+细胞。此外,通过角膜荧光素染色评估清创后上皮伤口闭合情况。

结果

在治疗 2 周后,Trap/F6H8 与 Trap 一样有效抑制角膜血管生成和淋巴管生成。在治疗 3 天后,Trap/F6H8 在抑制角膜血管生成方面甚至比 Trap 更有效。两种治疗组(Trap/F6H8 和 Trap)均显著减少角膜 CD45+细胞募集。Trap/F6H8 或 Trap 对清创后的上皮闭合无影响。

结论

在这项研究中,我们证明 F6H8 是一种将 VEGF Trap 局部递送至角膜新生血管化的潜在载体。我们的发现可能为角膜局部抗血管生成治疗开辟新的治疗途径,因为 F6H8 已获准用于眼部表面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/eb6dd0fd1e88/tvst-9-11-15-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/db3a817c1660/tvst-9-11-15-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/7ba03de468de/tvst-9-11-15-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/0cda8c563864/tvst-9-11-15-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/eb6dd0fd1e88/tvst-9-11-15-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/db3a817c1660/tvst-9-11-15-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/7ba03de468de/tvst-9-11-15-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/0cda8c563864/tvst-9-11-15-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bcc/7571278/eb6dd0fd1e88/tvst-9-11-15-f004.jpg

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