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

光折射角膜手术后角膜伤口愈合的分子机制

• 批准号: 11557127
• 负责人: YAMASHITA Hidetoshi
• 金额: $ 8.64万
• 依托单位: Deparmtnent of Ophthalmology, Yamagata University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557127/
• 关键词: Excimer Laser; Cornea; Refractive Surgery; extracellular matrix; cytokines; TGF-β; hyalutonan; intracellular signal transduction; 屈折矯正手術; コラーゲン; hsp47; TGF-βシグナル伝達; ステロイド療法

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

在拍照手术后，发生角膜伤口愈合过程。在这一过程中，形成了疤痕和分布视觉。在这项研究中，我们使用了准分子激光角膜切除术模型后的角膜伤口愈合来研究新的细胞外基质（ECM）形成。我们在这项研究中的重点是转化生长因子-β（TGF-β）在伤口愈合中的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受体）发挥其作用，从而激活SMAD家族信号传感器。使用培养的细胞衍生的牛角膜，TGF-β通过包括TGF-β受体和SMAD家族透射剂在内的途径刺激了ECM蛋白质的产生和透明质酸合酶（HAS）活性。在临时激光磨损模型中的伤口愈合过程中，伤口周围的角膜上皮细胞增殖，迁移并覆盖了磨损的区域。在再生的上皮下，角膜细胞首先消失，然后重新流行……更挑选了前角膜基质，并参与了上皮下ECM形成的形成。在此过程中，将角膜细胞激活并招募到伤口部位。在组织重塑期间，活化的角膜细胞和ECM异常消失。在伤口愈合过程中，3种TGF-β同工型（TGF-β1，β2，β3），2种TGF-β受体的2种类型，SMAD家族成员在再生上皮细胞和活化的角化角膜细胞中的增加，这表明TGF-β已产生并通过包括SMADS（包括SMADS）在内的伤口愈合。这些反应被中和TGF-β的抗体处理阻塞。在同工型中，抗TGF-β1抗体的阻断作用很重要。综上所述，它被指定为TGF-β1是激活和募集角膜细胞在精确剂激光角膜切除术后在角膜基质中产生ECM的主要参与者，并且在3种同工型之间的功能不同。该过程与TGF-β直接相关，其中机理仍有待解决。较少的

项目成果

Usui T, Amano S, Oshika T, Suzuki K, Miyata K, Araie M,Heldin P,Yamashita H: "Expression regulation of hyaluronan synthase(HAS)in corneal endothelial cells"Invest Ophthalmol Vis Sci. 41. 3261-3267 (2000)

Usui T、Amano S、Oshika T、Suzuki K、Miyata K、Araie M、Heldin P、Yamashita H：“角膜内皮细胞中透明质酸合酶 (HAS) 的表达调节”Invest Ophasemol Vis Sci。

Obata H, Yamashita H et al: "Expression of TGF-β superfamily receptors in rat eye."Acta Ophthalmol. 77. 151-156 (1999)

Obata H、Yamashita H 等人：“大鼠眼中 TGF-β 超家族受体的表达”。Acta Ophamol。77. 151-156 (1999)

Mita T Yamashita H , Kaji Y , Obata H, Hanyu A, Suzuki M, Tobari I: "Functional difference of TGF-β isoforms regulating corneal wound healing after excimer laser keratectomy"Exp Eye Res. 68. 513-519 (1999)

Mita T Yamashita H、Kaji Y、Obata H、Hanyu A、Suzuki M、Tobari I：“准分子激光角膜切除术后调节角膜伤口愈合的 TGF-β 亚型的功能差异”Exp Eye Res。

Mita T, Yamashita H et al: "Functional difference of TGF-β isoforms reglulating corneal wound healing after excimer laser keratectomy."Exp Eye Res. 68. 513-519 (1999)

Mita T、Yamashita H 等人：“准分子激光角膜切除术后调节角膜伤口愈合的 TGF-β 亚型的功能差异。”Exp Eye Res. 68. 513-519 (1999)

Obata H,Yamashita H et al.: "Expression of TGF-β superfamily receptors in rat eyes."Acta Ophthalmal. 77. 151-156 (1999)

Obata H、Yamashita H 等：“大鼠眼中 TGF-β 超家族受体的表达”。《眼科学报》77. 151-156 (1999)。