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研究生:馬惠康
研究生(外文):David Hui-Kang Ma
論文名稱:眼表層細胞、胞外間質與基底膜在調控角膜血管生成所扮演角色之研究
論文名稱(外文):The Study of the Role of Ocular Surface Cells, Extracellular Matrix, and Basement Membrane in the Regulation of Corneal Angiogenesis
指導教授:陳君侃陳君侃引用關係蔡瑞芳蔡瑞芳引用關係
指導教授(外文):Jan-Kan ChenRay Jui-Fang Tsai
學位類別:博士
校院名稱:長庚大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2000
畢業學年度:88
語文別:中文
論文頁數:94
中文關鍵詞:角膜結膜輪部血管生成纖維母細胞金屬蛋白脢金屬蛋白脢組織抑制劑羊膜
外文關鍵詞:CorneaConjunctivaLimbusAngiogenesisFibroblastMatrix metalloproteinaseTissue inhibitor of metalloproteinaseAmniotic membrane
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中文摘要
在廿世紀的最後十年中,在眼表層的基礎及臨床研究上均有很大的進展。其中,(1)輪部幹細胞(角膜表皮細胞的來源)觀念的建立及臨床運用(2)表皮-基質交互作用分子機轉的了解,以及(3)利用羊膜移植做為基質替換,以促進傷口癒合,以及眼表層表皮之分化,是三項最重要的發現,且為改善眼表層重建手術的效果奠下良好之基礎。同時關係到上述三大主題的一個重要議題,便是要了解眼表層如何控制發炎反應及血管生成作用,從而維持角膜的無血管及免疫豁免權,以及結膜及角膜表皮的正常生長與分化。
利用改良自吾人以往研究表皮-基質交互作用的細胞共同培養模式,吾人已顯示輪部-角膜表皮細胞具有抑制血管生成作用。除了其他已知的存在於眼角膜中的血管生成抑制劑外,吾人亦找到第四型金屬蛋白脢組織抑制劑(TIMP-4)存在於角膜細胞的證據。然而,由於體外細胞培養系統無法真正反應活體角膜血管生成作用,吾人進一步研究了在角膜血管生成作用中,基質金屬蛋白脢(MMP)及金屬蛋白脢組織抑制劑之表現與發炎反應的相關性。最後,發現人類羊膜含有抗血管生成及抗發炎因子,有助於吾人了解羊膜抗血管生成/抗發炎之機轉。
During the last decade of the 20th century, there was a great advancement both in the basic and clinical research of ocular surface diseases. Among them, (1) the establishment and clinical application of limbal stem cell (progenitor of corneal epithelial cells) concept, (2) the understanding of the molecular mechanisms of epithelial-stromal interactions and its consequences, and (3) using amniotic membrane (AM) transplantation as substrate replacement to promote wound healing and differentiation of ocular surface epithelial cells were the most important achievements, and have paved the way for improved outcome of ocular surface reconstruction surgeries. A pivotal issue concerning the three major topics is to understand the mechanisms by which the non-inflammatory nature of the ocular surface is maintained so as to maintain the avascularity and immune privilege of the cornea, and normal proliferation of conjunctival and corneal epithelial cells.
By using modified coculture model from our previous epithelial-stromal interaction study, we have demonstrated the anti-angiogenic activity of limbo-corneal epithelial cells. In addition to other known anti-angiogenic factors in cornea, we also found pieces of evidence for the presence of tissue inhibitors of metalloproteinase (TIMP) - 4 in corneal cells. Since events found in in vitro system can not fully reflect the in vivo corneal angiogenesis, we further studied the correlation of matrix metalloproteinase (MMP) and TIMP expression with the severity of inflammation during corneal neovascularization. Finally, the identification of anti-angiogenic and anti-inflammatory proteins in human AM helps to understand the anti-angiogenic/inflammatory mechanism expressed by AM.
封面
目錄
指導教授推薦書
口試委員會審定書
誌謝
中文摘要
英文摘要
第一章 緒論與文獻回顧
第二章 眼表層細胞之體外促進血管生成作用
引言與目的
材料與方法
結果
討論
第三章 第四型金屬蛋白脢組織抑制劑 ( TIMP-4 )在正常人體角膜細胞及大白鼠角膜新生血管之表現
引言與目的
材料與方法
結果
討論
第四章 燒灼及縫線導致之角膜新生血管中 MMP- 2、MMP- 9 及 TIMP- 1、- 2、及- 3表現之比較
引言與目的
材料與方法
結果
討論
第五章 保存羊膜之抗血管生成活性的研究 -- 辨識人類羊膜中之抗血管生成及抗發炎蛋白
引言與目的
材料與方法
結果
討論
第六章 結論與未來之展望
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