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

Abstract

Background: 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 antiangiogenesis, but its role in CNV has not yet been investigated. Methods: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 inflammationrelated molecules were quantified via immunohistochemical (IHC) analysis and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Murine peritoneal macrophages were used in vitro to further verify the effect of melatonin in inflammatory CNV.Results: 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.Conclusions: Melatonin inhibits the neovascular and inflammatory responses in corneal alkali burn injury, suggesting that it may be a potential therapy for CNV.

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“…Following the aforementioned procedures, 35 total RNA was extracted by employing the Total RNA extraction kit (R1200, Solarbio, Beijing, China) from myocardial tissue homogenate or RAW264.7 cells and reverse-transcribed to cDNA by adopting an RNA reverse transcription kit (4387406, Invitrogen). qPCR was conducted on ABI Prism 7300 system (ABI, Foster City, CA, USA) under the following conditions: 30 s at 95 C, and 40 cycles of 5 s at 95 C, 30 s at 59 C, and 30 s at 72 C. The 2 ÀΔΔCT method was adopted to analyze the relative expression of genes with β-actin as a reference gene.…”

The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina

“…In vitro experiments using murine peritoneal macrophages confirmed melatonin’s inhibitory effect on these factors. These findings suggest that melatonin can suppress angiogenesis in alkali-injured corneas by inhibiting macrophage infiltration and the secretion of proangiogenic and inflammatory factors [ 55 ]. The potential therapeutic benefits of melatonin as an anti-inflammatory agent extended to corneal transplantation.…”