Moromizato Y, Stechschulte S, Miyamoto K, Murata T, Tsujikawa A, Joussen A M, Adamis A P
Laboratory for Surgical Research, Children's Hospital, Harvard Medical School, and the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Am J Pathol. 2000 Oct;157(4):1277-81. doi: 10.1016/S0002-9440(10)64643-3.
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 were similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively. When VEGF mRNA levels were analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% (n = 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.
广泛的角膜缘损伤是不可逆性失明的主要原因。角膜缘干细胞的破坏常导致角膜新生血管形成和光学性能较差的上皮。先前的研究表明，角膜缘损伤后的新生血管形成依赖血管内皮生长因子（VEGF），其中大部分VEGF来自侵入角膜的炎症细胞。利用相关的角膜缘损伤小鼠模型，我们研究了CD18和细胞间黏附分子-1（ICAM-1）在角膜缘损伤诱导的新生血管形成中的作用。结果显示，与品系特异性正常对照相比，CD18缺陷小鼠和ICAM-1缺陷小鼠的新生血管形成分别减少了35%（n = 5，P = 0.003）和36%（n = 5，P = 0.002）。角膜中性粒细胞计数也分别同样减少了51%（n = 5，P < 0.003）和46%（n = 5，P < 0.006）。分析VEGF mRNA水平时，它们分别降低了66%（n = 3，P = 0.004）和48%（n = 3，P = 0.024）。综上所述，这些数据确定CD-18和ICAM-1是角膜缘损伤后炎症性和VEGF依赖性角膜新生血管形成的介质。靶向CD18和ICAM-1可能在治疗角膜及其他部位与炎症相关的新生血管形成中有用。
