Nintedanib Eye Drops Inhibit Alkali Burn-Induced Corneal Neovascularization Via RAP1/MEK/ERK Signaling Pathway.

Area of Science:

• Ophthalmology
• Vascular Biology
• Pharmacology

Background:

• Corneal neovascularization (CNV) is a pathological process that can lead to vision impairment.
• Alkali burns are a common cause of severe ocular injury, often resulting in CNV.
• Current treatments for CNV have limitations, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To investigate the efficacy of topical nintedanib (NTD) eye drops in treating alkali burn-induced CNV.
• To elucidate the underlying molecular mechanisms by which NTD affects CNV.

Main Methods:

• In vitro studies assessed NTD's effects on human umbilical vein endothelial cells (HUVECs) proliferation, migration, and tube formation.
• RNA sequencing identified gene expression changes following NTD treatment.
• In vivo studies utilized a mouse model of alkali burn-induced CNV, with topical NTD administration and subsequent histological and molecular analysis.

Main Results:

• NTD inhibited HUVEC proliferation, migration, and tube formation in vitro.
• RNA sequencing revealed enrichment of RAP1 and MAPK signaling pathways.
• NTD downregulated key pro-angiogenic factors including VEGFA, VEGFR2, and HIF-1α, and suppressed CNV, inflammation, and LYVE1/CD31 expression in vivo.

Conclusions:

• Topical nintedanib eye drops are effective in reducing alkali burn-induced corneal neovascularization.
• The therapeutic effect of NTD is mediated through the modulation of the RAP1/MEK/ERK signaling pathway.
• NTD represents a potential therapeutic strategy for managing CNV following alkali eye injury.