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

光折射手术后，角膜伤口会发生愈合过程。在这个过程中，疤痕形成并干扰视力。在本研究中，我们利用准分子激光角膜切除术后角膜伤口愈合模型来研究新的细胞外基质（ECM）的形成。我们本研究的重点是转化生长因子-β (TGF-β) 在伤口愈合中 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）发挥作用，激活 Smad 家族信号转导器。使用牛角膜培养细胞，TGF-β 通过 TGF-β 受体和 Smad 家族传感器等途径刺激 ECM 蛋白产生和透明质酸合酶 (HAS) 活性。在准分子激光磨损模型的伤口愈合过程中，伤口周围的角膜上皮细胞增殖、迁移并覆盖磨损区域。在再生的上皮下，角膜细胞首先消失然后重新流行，形成前角膜基质并参与上皮下ECM的形成。在此过程中，角膜细胞被激活并募集到伤口部位。此后，激活的角膜细胞和异常的 ECM 在组织重塑过程中消失。在伤口愈合过程中，再生上皮和活化的角膜细胞中3种TGF-β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Smads等途径产生并影响伤口愈合过程。这些反应被中和 TGF-β 的抗体治疗所阻断。 TGF-β1 抗体的阻断作用在同工型中最为显着。综上所述，准分子激光角膜切除术后，TGF-β1是激活和募集角膜基质细胞产生ECM的主要参与者，并且3种异构体的功能有所不同。这一过程与TGF-β直接相关，其机制仍有待解决。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。

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。

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)

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)。

Obata H, Kaji Y, Yamada H, Kato M, Tsuru T,Yamashita H: "Expression of transforming growth factor-β superfamily receptors in rat eye"Acta Ophthalmol. 77. 151-156 (1999)

Obata H、Kaji Y、Yamada H、Kato M、Tsuru T、Yamashita H：“大鼠眼中转化生长因子-β 超家族受体的表达” Acta Ophamol. 77. 151-156 (1999)