Kao W W, Kao C W, Kaufman A H, Kombrinck K W, Converse R L, Good W V, Bugge T H, Degen J L
Department of Ophthalmology, University of Cincinnati, OH 45267-0527, USA.
Invest Ophthalmol Vis Sci. 1998 Mar;39(3):502-8.
The local deposition of fibrinogen and other plasma products from tears within corneal wounds and the expression of plasminogen activator by corneal epithelial cells suggest that the coagulation and fibrinolytic systems play an important role in corneal wound healing. The authors used mouse lines deficient in plasminogen (Plg), fibrinogen (Fib), or both to elucidate the roles of these key fibrinolytic and coagulation factors in the healing of corneal epithelial defects.
Mice were anesthetized, and corneal epithelial defects (3 mm) were created with a blade. The authors conducted histologic examination and immunohistochemical analysis on the healing of injured corneas.
The corneal epithelial defects of wild-type mice with transparent corneas healed quickly in 7 days, whereas the healing of plasminogen-deficient mice was impaired and complicated by severe and persistent inflammatory responses, the formation of retrocorneal fibrin deposits, corneal cloudiness caused by scar-tissue formation, and often stromal neovascularization. To determine whether these defects in corneal wound repair were specifically related to an impediment in fibrinolysis, corneal wound healing was compared in mice with a combined deficiency in plasminogen and fibrinogen. The loss of fibrinogen in mice lacking plasminogen resulted in the restoration of normal healing with transparent corneas in 7 days, similar to that of wild-type mice.
These results provide direct evidence that hemostatic factors play a crucial role in corneal wound repair despite the lack of local hemorrhage. Furthermore, they demonstrate that the essential role of plasmin in corneal would healing is fibrinolysis. It prevents the adverse inflammatory responses caused by prolonged fibrin and fibrinogen deposition in injured corneas.
角膜伤口处泪液中纤维蛋白原及其他血浆产物的局部沉积，以及角膜上皮细胞中纤溶酶原激活物的表达，提示凝血和纤溶系统在角膜伤口愈合中起重要作用。作者使用缺乏纤溶酶原（Plg）、纤维蛋白原（Fib）或两者均缺乏的小鼠品系，以阐明这些关键纤溶和凝血因子在角膜上皮缺损愈合中的作用。
将小鼠麻醉，用刀片造成3毫米的角膜上皮缺损。作者对受伤角膜的愈合情况进行了组织学检查和免疫组化分析。
角膜透明的野生型小鼠的角膜上皮缺损在7天内迅速愈合，而缺乏纤溶酶原的小鼠愈合受损，并伴有严重且持续的炎症反应、角膜后纤维蛋白沉积物的形成、瘢痕组织形成导致的角膜混浊，且常伴有基质新生血管形成。为了确定角膜伤口修复中的这些缺陷是否与纤溶障碍有特定关系，作者比较了纤溶酶原和纤维蛋白原联合缺乏的小鼠的角膜伤口愈合情况。缺乏纤溶酶原的小鼠中纤维蛋白原的缺失导致角膜在7天内恢复正常愈合且保持透明，与野生型小鼠相似。
这些结果提供了直接证据，表明尽管缺乏局部出血，但止血因子在角膜伤口修复中起关键作用。此外，它们表明纤溶酶在角膜伤口愈合中的重要作用是纤溶作用。它可防止受伤角膜中纤维蛋白和纤维蛋白原长期沉积引起的不良炎症反应。
