Forkhead Domain Inhibitor-6 Suppresses Corneal Neovascularization and Subsequent Fibrosis After Alkali Burn in Rats.
Forkhead Domain Inhibitor-6 Suppresses Corneal Neovascularization and Subsequent Fibrosis After Alkali Burn in Rats.
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Forkhead Domain Inhibitor-6 抑制大鼠碱烧伤后角膜新生血管形成和随后的纤维化
DOI：
10.1167/iovs.63.4.14
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发表时间：
2022-04-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究旨在探讨Forkhead Domain inhibital6 （FDI-6）对碱烧伤引起的炎症性角膜血管生成及随后纤维化的调节作用。采用NaOH建立大鼠角膜碱烧伤模型，并用FDI-6（40µM）或对照物局部处理大鼠眼睛，每天4次，连续7 d。在裂隙灯显微镜下观察角膜碱烧伤后第1、4、7天角膜新生血管形成、炎症及上皮缺损。在第7天进行血管生成、炎症和纤维化相关指标分析。采用小鼠巨噬细胞（RAW264.7细胞）和小鼠视网膜微血管内皮细胞（MRMECs）检测FDI-6对体外炎性血管生成的影响。外用FDI-6可显著减轻碱烧伤引起的角膜炎症、新生血管和纤维化。FDI-6抑制碱损伤角膜血管生成因子（血管表皮生长因子、CD31、基质金属蛋白酶-9、内皮NO合成酶）、纤维化因子（α-平滑肌肌动蛋白、纤维连接蛋白）、促炎因子白细胞介素-6的表达。FDI-6下调RAW264.7细胞单核细胞趋化蛋白-1、促炎细胞因子（白细胞介素-1β和肿瘤坏死因子α）、核苷酸结合寡聚结构域样受体家族含pyrin结构域3和血管内皮生长因子的表达，抑制MRMECs体外增殖、迁移和成管。FDI-6可以减轻碱损伤角膜的新生血管、炎症和纤维化。
The purpose of this study was to investigate the effects of Forkhead Domain Inhibitor-6 (FDI-6) on regulating inflammatory corneal angiogenesis and subsequent fibrosis induced by alkali burn. A corneal alkali burn model was established in Sprague Dawley rats using NaOH and the rat eyes were topically treated with FDI-6 (40 µM) or a control vehicle four times daily for 7 days. Corneal neovascularization, inflammation and epithelial defects were observed on days 1, 4, and 7 under a slit lamp microscope after corneal alkali burn. Analysis of angiogenesis-, inflammation-, and fibrosis-related indicators was conducted on day 7. Murine macrophages (RAW264.7 cells) and mouse retinal microvascular endothelial cells (MRMECs) were used to examine the effects of FDI-6 on inflammatory angiogenesis in vitro. Topical delivery of FDI-6 significantly attenuated alkali burn-induced corneal inflammation, neovascularization, and fibrosis. FDI-6 suppressed the expression of angiogenic factors (vascular epidermal growth factor, CD31, matrix metalloproteinase-9, and endothelial NO synthase), fibrotic factors (α-smooth muscle actin and fibronectin), and pro-inflammatory factor interleukin-6 in alkali-injured corneas. FDI-6 downregulated the expression of monocyte chemotactic protein-1, pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-alpha), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3, and vascular endothelial growth factor in RAW264.7 cells and inhibited the proliferation, migration, and tube formation of MRMECs in vitro. FDI-6 can attenuate corneal neovascularization, inflammation, and fibrosis in alkali-injured corneas.
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影响因子：
2.1
作者：
Laria, C;Alio, JL;RuizMoreno, JM
通讯作者：
RuizMoreno, JM
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
影响因子：
9.8
作者：
Makanya, Andrew N.;Hlushchuk, Ruslan;Djonov, Valentin G.
通讯作者：
Djonov, Valentin G.
影响因子：
4.4
作者：
Ferrari, Giulio;Hajrasouliha, Amir R.;Dana, Reza
通讯作者：
Dana, Reza
影响因子：
4.8
作者：
Cheng, Cheng-I;Chen, Po-Han;Kao, Ying-Hsien
通讯作者：
Kao, Ying-Hsien