Melatonin exerts anti-angiogenic and anti-inflammatory effects in alkali-burned corneas

• Published in: Annals of translational medicine Vol. 10; no. 8; p. 432
• Main Authors: Meng, Jie, Lin, Bingying, Huang, Siyu, Li, Yangyang, Wu, Pengsen, Zhang, Fan, Ke, Yu, Hei, Xiangqing, Huang, Danping
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 01.04.2022
• Subjects: Original; macrophage; alkali burn injury; melatonin; inflammation; Corneal neovascularization (CNV)
• ISSN: 2305-5839; 2305-5839
• DOI: 10.21037/atm-21-4927

Corneal neovascularization (CNV) caused by alkali burn injury is tightly associated with an inflammatory reaction and can lead to vision loss. Melatonin is involved in anti-inflammation and anti-angiogenesis, but its role in CNV has not yet been investigated. We induced CNV using sodium hydroxide (NaOH) and compared the reactions of vehicle control and melatonin-treated male C57BL/6 mice at 7 and 14 days following the corneal burn. The infiltration of inflammatory cells and the expression of proangiogenic factors, chemokines, and inflammation-related molecules were quantified via immunohistochemical (IHC) analysis and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Murine peritoneal macrophages were used to further verify the effect of melatonin in inflammatory CNV. Compared with the vehicle control mice, the melatonin-treated mice showed significant inhibition of angiogenesis and reduction of corneal epithelial defects in alkali-burned corneas. Concomitantly, the infiltration of inflammatory cells and F4/80 cells were dramatically reduced after melatonin treatment. The messenger RNA (mRNA) expression of proangiogenic factors [vascular endothelial growth factors (VEGF) and matrix metalloproteinase-9 (MMP-9)], monocyte chemotactic protein-1 (MCP-1), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) and IL-6] were down-regulated in the melatonin-treated mice. Moreover, melatonin inhibited the expression of these factors in murine peritoneal macrophages. Melatonin inhibits the neovascular and inflammatory responses in corneal alkali burn injury, suggesting that it may be a potential therapy for CNV.