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Updated: Mar 21, 2026
An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse
Published on: April 7, 2014
Nintedanib Eye Drops Inhibit Alkali Burn-Induced Corneal Neovascularization Via RAP1/MEK/ERK Signaling Pathway
Jingfan Li1, Ge Zhang1, Jiake Li1
1Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Purpose:
To investigate the effect of topical nintedanib (NTD) eye drops on alkali burn-induced corneal neovascularization (CNV) and the mechanisms involved.
Methods:
The effects of NTD on the proliferation, migration, and tube-like structure formation assays were evaluated in human umbilical vein endothelial cells (HUVECs). RNA sequencing was performed to identify differentially expressed genes following NTD treatment. The expression of the RAP1A/MEK/HIF-1α axis was assessed by immunofluorescence (IF) and western blotting in HUVECs after NTD treatment. A CNV mouse model was established, and topically administered NTD eye drops three times daily for 10 consecutive days. Hematoxylin and eosin staining and IF were performed on days 3 and 7 after modeling. CNV was quantitatively analyzed after cardiac perfusion on day 10.
Results:
In vitro, NTD inhibited the proliferation, migration, and tube-like structure formation of HUVECs. RAP1 and MAPK signaling pathways were enriched by RNA sequencing analysis. NTD downregulated the expressions of RAP1A, p-MEK, p-ERK1/2, HIF-1α, VEGFA, and VEGFR2 in VEGF-stimulated HUVECs. In vivo, NTD eye drops demonstrated appropriate osmolarity and pH values. Compared to the control and vehicle groups, NTD eye drops suppressed CNV, inflammation, and the expression of LYVE1, CD31, VEGFA, and RAP1 in the cornea.
Conclusions:
Topical NTD administration effectively reduced alkali burn-induced CNV, which was related to the RAP1/MEK/ERK pathway. NTD could be an effective treatment strategy for CNV post-alkali injury.
Insights
Topical nintedanib (NTD) eye drops effectively reduced corneal neovascularization (CNV) after alkali burns by inhibiting endothelial cell function via the RAP1/MEK/ERK pathway. This suggests NTD is a promising treatment for post-injury CNV.
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.
