Mita T, Yamashita H, Kaji Y, Obata H, Yamada H, Kato M, Hanyu A, Suzuki M, Tobari I
Department of Ophthalmology, Toho University School of Medicine, Tokyo, Japan.
Graefes Arch Clin Exp Ophthalmol. 1998 Nov;236(11):834-43. doi: 10.1007/s004170050168.
Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process.
The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade.
At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days.
TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.
转化生长因子β（TGF-β）调节细胞外基质沉积、细胞增殖和迁移，并在角膜中表达。TGF-β被认为参与角膜伤口愈合过程。
使用准分子激光的PTK模式切除Lewis大鼠的中央角膜区域（直径3毫米），并在治疗后12小时和24小时以及2、5、10和30天观察伤口愈合过程。采用免疫组织化学方法研究TGF-β1、-β2和-β3、TGF-βⅠ型和Ⅱ型受体、α3、α5、β4整合素亚基、层粘连蛋白和纤连蛋白的表达。在激光治疗后，每天腹腔注射50微克中和TGF-β1、-β2和-β3的抗体，持续5天，以研究TGF-β功能阻断的作用。
在再生上皮的前沿，24小时后未表达TGF-βⅠ型和Ⅱ型受体以及β4整合素亚基。2天后再生上皮覆盖了切除区域。上皮下区域形成了异常的纤维化层。该层在早期（激光切除后2 - 5天）的基质中含有圆形细胞，10天后含有梭形的成纤维细胞样角膜细胞。层粘连蛋白和纤连蛋白在纤维化层中的表达增加。增加的基质细胞表达TGF-β异构体和TGF-β受体。中和TGF-β可抑制激光切除区域5天后基质细胞的增加。
在大鼠模型中，准分子激光切除后角膜伤口愈合过程中，TGF-β可能参与上皮细胞迁移和基质细胞反应。
