TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization.

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.