The function of mast all Chymase to corneal disorders in vernal keratoconjunctivitis

我们测定了春性角膜结膜炎患者泪液中肥大细胞乳糜酶活性的水平。在VKC患者的泪液中检测到高的乳糜酶活性。这些活性程度与VKC严重程度显著相关（r=0.9245, p<0.001）。接下来，我们在体外研究了酶对角膜上皮细胞的影响。Chymase引起occludin和纤连蛋白的蛋白水解，导致角膜上皮细胞屏障功能下降，迁移受到抑制。此外，切酶还能从角膜上皮细胞产生的细胞外基质中释放并激活TGF-β_1。释放TGF-β_1向角膜肌成纤维细胞转化。角膜肌成纤维细胞产生大量干细胞因子。干细胞因子是肥大细胞的重要分子，在肥大细胞的增殖、成熟和趋化过程中起着至关重要的作用。我们推测存在一个正反馈回路，在这个正反馈回路中，淀粉酶通过TGF-β_1将角化细胞分化为肌成纤维细胞，肌成纤维细胞又通过SCF刺激肥大细胞。我们的研究结果表明，靶向乳糜酶可能减轻VKC角膜并发症的严重程度。特异性的酶抑制剂将在未来问世。

We determined the level of mast cell chymase activity in the tears of patients with vernal keratoconjunctivitis. High chymase activity was detected in the tear of VKC patients. The degree of these activity correlated significantly with VKC severity (r=0.9245, p<0.001).Next, we investigated the in vitro effects of chymase on corneal epithelial cells. Chymase caused the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of migration of corneal epithelial cells. In addition, chymase released and activated TGF-β_1 from extracellular matrix produced by corneal epithelial cell. Released TGF-β_1 transdifferentiated keratocytes to corneal myofibroblasts. Corneal myofibroblasts produced a large amount of stem cell factor. Stem cell factor is an important molecule, which has a crucial role in proliferation, maturation and chemotaxis for mast cell. We speculate the existence of a positive feed-back loop in which chymase differentiate keratocyte to myofibroblasts via TGF-β_1 , and myofibroblasts in turn stimulate mast cell via SCF.The findings of our study that targeting chymase may lessen the severity of corneal complications in VKC. Specific inhibitors of chymase should become available in the future.