MOLECULAR MECHANISMS OF CORNEAL WOUND HEALING AFTER PHOTO-REFRACTIVE CORNEAL SURGERY

屈光手术后，发生角膜伤口愈合过程。在这个过程中，疤痕形成并干扰视力。本研究利用准分子激光角膜切削术后角膜创面愈合的模型，探讨新的细胞外基质（ECM）的形成。本研究的重点是转化生长因子-β（TGF-β）在创伤愈合过程中ECM形成中的作用。TGF-β通过两种类型的丝氨酸/苏氨酸激酶受体（II型和I型受体）发挥其作用，其激活Smad家族信号转导子。利用牛角膜细胞培养，TGF-β通过TGF-β受体和Smad家族转导子等途径刺激ECM蛋白的产生和透明质酸合成酶（HAS）的活性。在准分子激光擦伤模型的创面愈合过程中，创面周围的角膜上皮细胞增殖、迁移并覆盖擦伤区域。在再生上皮下，角膜基质细胞先消失，然后重新突起 ...更多信息 形成角膜前基质，并参与上皮下ECM的形成。在这个过程中，角膜细胞被激活并募集到伤口部位。活化的角膜基质细胞和异常的ECM在组织重塑过程中消失。在创伤愈合过程中，再生上皮和活化的角膜基质细胞中TGF-β 3种亚型（TGF-β1、β2、β3）、2种TGF-β受体、Smad家族成员的表达增加，表明TGF-β通过包括Smads在内的途径产生并影响创伤愈合过程。这些反应通过用中和TGF-β的抗体处理而被阻断。TGF-β1抗体对各亚型的阻断作用不明显。结论：TGF-β1是准分子激光角膜切削术后角膜基质中激活和募集角膜基质细胞产生ECM的主要因素，且3种亚型的作用不同。该过程与TGF-β直接相关，其机制尚待解决。少

After photo-refractive surgery, the corneal wound healing process occurs. Suring this process, the scar is formed and disturbs vision. In this study, we used the corneal wound healing after excimer laser keratectomy model to investigate the new extracellular matrix(ECM)formation. Our focus in this study is the role(s)of transforming growth factor-β(TGF-β)in the ECM formation in wound healing. TGF-β exerts its effects through two types of serine/threonine kinase receptors (type II and I receptors), which activate Smad family signal transducers. Using the cultured cells derived bovine cornea, TGF-β stimulated ECM protein production and hyaluronan synthase(HAS)activity through the pathways including TGF-β receptors and Smad family transducers. In the wound healing process in the excimer laser abrasion model, the corneal epithelial cells surrounding the wound proliferated, migrated and covered the abraded area. Under the regenerated epithelium, keratocytes first disappeared and then re-pop … More ulated the anterior corneal stroma and were involved in the formation of subepithelial ECM formation. In this process, the keratocytes were activated and recruited into the wound site. The activated keratocytes and abnormal ECM thereafter disappeared during tissue remodelling. During the wound healing process, the expression of 3 TGF-β isoforms(TGF-β1, β2, β3), 2 types of TGF-β receptors, Smad family members increased in the regenerating epithelium and the activated keratocytes, which shows that TGF-β is produced and affects wound healing process through the pathways including Smads. These responses were blocked by the treatment with the antibodies neutralizing TGF-β. Blocking effects by antibody to TGF-β1 was modt significant among the isoforms. Taken together, it is spechlated the TGF-β1 is the main player to activate and recruit the keratocytes to produce ECM in the corneal stroma after excimer laser keratectomy, and the functions are different among 3 isoforms. This process was correlated directly with TGF-β, of which the mechanisms remains to be resolved. Less