CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury

CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury
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DOI:
10.1016/s0002-9440(10)64643-3
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发表时间:
2000-10-01
影响因子:
6
通讯作者:
Adamis, AP
Adamis, AP
中科院分区:
医学2区
文献类型:
--
作者:
Moromizato, Y;Stechschulte, S;Adamis, AP

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广泛的角膜缘损伤是导致不可逆失明的主要原因。角膜缘干细胞的破坏通常导致角膜新生血管和光学下上皮,先前的研究表明,角膜缘损伤后的新生血管依赖于血管内皮生长因子(VEGF),其中大部分VEGF来自侵入角膜的炎症细胞。我们检测了CD18和细胞间粘附分子-1 (ICAM-1)在角膜缘损伤诱导的新生血管形成中的作用,结果表明,CD18和ICAM-1缺失小鼠的新生血管形成分别比正常小鼠少35% (n = 5,P = 0.003)和36% (n = 5,P = 0.002)。角膜中性粒细胞计数也同样减少了51% (n = 5, P < 0.003)和46% (n = 5, P < 0.006),当VEGF mRNA水平进行分析时,它们分别减少了66% (n = 3, P = 0.004)和48% (n = 3, P = 0.024)。综上所示,这些数据表明CD-18和ICAM-1是角膜边缘损伤后炎症和VEGF依赖性角膜新生血管形成的介质。靶向CD18和ICAM-1可能有助于治疗角膜和其他部位炎症相关的新生血管。
Extensive Limbal injury is a leading cause of irreversible blindness. The destruction of corneal limbal stem cells often results in corneal neovascularization and an optically inferior epithelium, Previous work has shown that the neovascularization after limbal injury is vascular endothelial growth factor (VEGF)-dependent, with much of the VEGF emanating from the inflammatory cells that invade the cornea, Using a relevant mouse model of limbal injury, we examined the role of CD18 and intercellular adhesion molecule-1 (ICAM-1) in limbal injury-induced neovascularization, The results show that CD18- and ICAM-1-deficient mice developed 35% (n = 5,P = 0.003) and 36% (n = 5, P = 0.002) less neovascularization than strain-specific normal controls, respectively. The corneal neutrophil counts mere similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively, When VEGF mRNA levels mere analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% Of = 3,p = 0.024), respectively, Taken together, these data identify CD-18 and ICAM-1 as mediators of the inflammatory and VEGF-dependent corneal neovascularization that follows limbal injury. The targeting of CD18 and ICAM-1 may prove useful in the treatment of inflammation-associated neovascularization in the cornea and elsewhere.