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Updated: Sep 19, 2025
Author Spotlight: Decoding Corneal Neovascularization with Alkali Burn Model for Future Therapeutic Strategies
Published on: June 30, 2023
TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization
Cong Xia1, Yan Deng2, Yichen Lu3
1Department of Ophthalmology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China; Department of Pathology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, 341000, Jiangxi Province, PR China.
Abstract:
Toll-like receptor 4 (TLR4), recognized as a fundamental mediator of inflammatory signaling, plays a crucial role in orchestrating the inflammatory response. Previous studies suggested that TLR4 knockout (KO) notably reduced corneal vascular areas induced by silver nitrate burn based on the morphological observation. The current study seeks to elucidate the influence of TLR4 signaling on corneal neovascularization (CNV) and to examine the underlying mechanisms. The model of alkali burn (AB)-induced CNV was built using TLR4 KO and wildtype (WT) mice. CNV was detected using a slit lamp. Corneal thickness was evaluated using H&E staining. The expression levels of VEGF-A, MyD88, and NF-κB were evaluated employing Western blot analysis, immunohistochemistry, and Real-time PCR techniques. The inflammation factors, IL-1β, TNF-α, and IL-6, were quantified using Real-time PCR. In addition, Resatorvid (Tak242), a specific inhibitor of TLR4, was used to treat AB cornea of WT mice. AB enhanced TLR4 signaling components, including MyD88 and NF-κB. TLR4 inhibition alleviated AB-induced corneal neovascularization and corneal thickness. The TLR4 signal, inflammatory factors and VEGF-A were also down-regulated. Our data indicated that TLR4 participated in the pathology of AB-induced CNV. TLR4 was over-expressed in the cornea of AB mice. TLR4 inhibition alleviated AB-induced CNV, and suppressed MyD88, NF-κB, VEGF-A, and inflammation factors. These findings may provide new insights for the clinical treatment of AB-induced CNV.
Insights
Toll-like receptor 4 (TLR4) signaling drives corneal neovascularization after alkali burns. Inhibiting TLR4 reduces this neovascularization, swelling, and inflammation, offering a potential therapeutic target for alkali burn-induced corneal damage.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Toll-like receptor 4 (TLR4) is a key mediator of inflammatory signaling.
- Previous research indicated TLR4 knockout reduced corneal vascularization after silver nitrate burns.
- The role of TLR4 in alkali burn-induced corneal neovascularization (CNV) requires further elucidation.
Purpose of the Study:
- To investigate the role of TLR4 signaling in alkali burn-induced CNV.
- To examine the underlying molecular mechanisms of TLR4 in this process.
- To evaluate the therapeutic potential of TLR4 inhibition.
Main Methods:
- Alkali burn (AB) model in Toll-like receptor 4 knockout (KO) and wildtype (WT) mice.
- Assessment of corneal neovascularization (CNV) via slit lamp examination.
- Evaluation of corneal thickness using H&E staining.
- Quantification of VEGF-A, MyD88, NF-κB, IL-1β, TNF-α, and IL-6 expression via Western blot, immunohistochemistry, and Real-time PCR.
- Treatment of AB corneas with Resatorvid (Tak242), a TLR4 inhibitor.
Main Results:
- Alkali burn significantly enhanced TLR4 signaling components, including MyD88 and NF-κB.
- TLR4 inhibition with Resatorvid (Tak242) alleviated AB-induced CNV and reduced corneal thickness.
- TLR4 inhibition suppressed the expression of inflammatory factors (IL-1β, TNF-α, IL-6) and VEGF-A.
- TLR4 was found to be over-expressed in the corneas of AB mice.
Conclusions:
- TLR4 signaling plays a critical role in the pathology of alkali burn-induced corneal neovascularization.
- TLR4 inhibition demonstrates therapeutic potential by mitigating CNV, inflammation, and corneal thickening.
- Targeting TLR4 may offer a novel strategy for treating alkali burn-induced corneal damage.
