CXCR3 deletion aggravates corneal neovascularization in a corneal alkali-burn model. (December 2022)

• Record Type: Journal Article
• Authors: Li, Shengguo; Shi, Shuizhen; Xia, Fan; Luo, Ban; Ha, Yonju; Luisi, Jonathan; Gupta, Praveena K.; Merkley, Kevin H.; Motamedi, Massoud; Liu, Hua; Zhang, Wenbo
• Is Part Of: Experimental eye research. Volume 225(2022)
• Publication Date: 2022-12
• Subjects: Corneal neovascularization -- Inflammation -- Alkali burn -- CXCR3; BM Bone marrow -- OCT Optical Coherence Tomography -- qRT-PCR Quantitative real-time polymerase chain reaction -- VEGF Vascular endothelial growth factor -- WT Wild type; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109265
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Corneal neovascularization can cause devastating consequences including vision impairment and even blindness. Corneal inflammation is a crucial factor for the induction of corneal neovascularization. Current anti-inflammatory approaches are of limited value with poor therapeutic effects. Therefore, there is an urgent need to develop new therapies that specifically modulate inflammatory pathways and inhibit neovascularization in the cornea. The interaction of chemokines and their receptors plays a key role in regulating leukocyte migration during inflammatory response. CXCR3 is essential for mediating the recruitment of activated T cells and microglia/macrophages, but the role of CXCR3 in the initiation and promotion of corneal neovascularization remains unclear. Here, we showed that the expression of CXCL10 and CXCR3 was significantly increased in the cornea after alkali burn. Compared with WT mice, CXCR3 −/− mice exhibited significantly increased corneal hemangiogenesis and lymphangiogenesis after alkali burn. In addition, exaggerated leukocyte infiltration and leukostasis, and elevated expression of inflammatory cytokines and angiogenic factor were also found in the corneas of CXCR3 −/− mice subjected to alkali burn. With bone marrow (BM) transplantation, we further demonstrated that the deletion of CXCR3 in BM-derived leukocytes plays a key role in the acceleration of alkali burn–induced corneal neovascularization. Taken together, our results suggest that upregulation of CXCR3 does not exhibit its conventional action as a proinflammatory cytokine but instead serves as a self-protective mechanism for the modulation of inflammation and maintenance of corneal avascularity after corneal alkali burn. Highlights: The expression of CXCL10 and CXCR3 is significantly increased in the cornea after alkali burn. CXCR3 −/− mice exhibit significantly increased corneal hemangiogenesis and lymphangiogenesis after alkali burn. CXCR3 deletion aggravates leukocyte infiltration, leukostasis and the expression of inflammatory cytokines and angiogenic factor after alkali burn. The deletion of CXCR3 in bone marrow-derived leukocytes plays a key role in the acceleration of alkali burn–induced corneal neovascularization.