請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46828
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林中天(Chung-Tien Lin) | |
dc.contributor.author | Kuang-Tzu Kuo | en |
dc.contributor.author | 郭廣慈 | zh_TW |
dc.date.accessioned | 2021-06-15T05:41:56Z | - |
dc.date.available | 2010-08-24 | |
dc.date.copyright | 2010-08-24 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-22 | |
dc.identifier.citation | Adamis AP, and Shima DT. The role of vascular endothelial growth factor in ocular health and disease. Retina 25: 111-118, 2005.
2. Ahmed A, Berati H, Nalan A, and Aylin S. Effect of bevacizumab on corneal neovascularization in experimental rabbit model. Clin Experiment Ophthalmol 37: 730-736, 2009. 3. Amano S, Rohan R, Kuroki M, Tolentino M, and Adamis AP. Requirement for vascular endothelial growth factor in wound- and inflammation-related corneal neovascularization. Invest Ophthalmol Vis Sci 39: 18-22, 1998. 4. Bahar I, Kaiserman I, McAllum P, Rootman D, and Slomovic A. Subconjunctival bevacizumab injection for corneal neovascularization. Cornea 27: 142-147, 2008. 5. Bock F, Konig Y, Kruse F, Baier M, and Cursiefen C. Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 246: 281-284, 2008. 6. Bock F, Onderka J, Rummelt C, Dietrich T, Bachmann B, Kruse FE, Schlotzer-Schrehardt U, and Cursiefen C. Safety profile of topical VEGF neutralization at the cornea. Invest Ophthalmol Vis Sci 50: 2095-2102, 2009. 7. Chaloin-Dufau C, Pavitt I, Delorme P, and Dhouailly D. Identification of keratins 3 and 12 in corneal epithelium of vertebrates. Epithelial Cell Biol 2: 120-125, 1993. 8. Chang JH, Gabison EE, Kato T, and Azar DT. Corneal neovascularization. Curr Opin Ophthalmol 12: 242-249, 2001. 9. Chee KY, Kicic A, and Wiffen SJ. Limbal stem cells: the search for a marker. Clin Experiment Ophthalmol 34: 64-73, 2006. 10. Chen JJ, and Tseng SC. Abnormal corneal epithelial wound healing in partial-thickness removal of limbal epithelium. Invest Ophthalmol Vis Sci 32: 2219-2233, 1991. 11. Chen WL, Lin CT, Lin NT, Tu IH, Li JW, Chow LP, Liu KR, and Hu FR. Subconjunctival injection of bevacizumab (avastin) on corneal neovascularization in different rabbit models of corneal angiogenesis. Invest Ophthalmol Vis Sci 50: 1659-1665, 2009. 12. Ciulla TA, and Rosenfeld PJ. Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. Curr Opin Ophthalmol 20: 158-165, 2009. 13. Crispin SM. The Cornea. In: Petersen-Jones SM, and Crispin SM, ed. BSAVA manual of small animal ophthalmology. British Small Animal Veterinary Association, Gloucester, 2002. 14. Cursiefen C, Hofmann-Rummelt C, Kuchle M, and Schlotzer-Schrehardt U. Pericyte recruitment in human corneal angiogenesis: an ultrastructural study with clinicopathological correlation. Br J Ophthalmol 87: 101-106, 2003. 15. Dastjerdi MH, Al-Arfaj KM, Nallasamy N, Hamrah P, Jurkunas UV, Pineda R, 2nd, Pavan-Langston D, and Dana R. Topical bevacizumab in the treatment of corneal neovascularization: results of a prospective, open-label, noncomparative study. Arch Ophthalmol 127: 381-389, 2009. 16. Donisi PM, Rama P, Fasolo A, and Ponzin D. Analysis of limbal stem cell deficiency by corneal impression cytology. Cornea 22: 533-538, 2003. 17. Dua HS, Joseph A, Shanmuganathan VA, and Jones RE. Stem cell differentiation and the effects of deficiency. Eye (Lond) 17: 877-885, 2003. 18. Dua HS, Saini JS, Azuara-Blanco A, and Gupta P. Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol 48: 83-92, 2000. 19. Erdurmus M, and Totan Y. Subconjunctival bevacizumab for corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 245: 1577-1579, 2007. 20. Espana EM, Di Pascuale MA, He H, Kawakita T, Raju VK, Liu CY, and Tseng SC. Characterization of corneal pannus removed from patients with total limbal stem cell deficiency. Invest Ophthalmol Vis Sci 45: 2961-2966, 2004. 21. Ferrara N, Hillan KJ, Gerber HP, and Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3: 391-400, 2004. 22. Goldberg MF, and Bron AJ. Limbal palisades of Vogt. Trans Am Ophthalmol Soc 80: 155-171, 1982. 23. Han YS, Lee JE, Jung JW, and Lee JS. Inhibitory effects of bevacizumab on angiogenesis and corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 247: 541-548, 2009. 24. Hicklin DJ, and Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23: 1011-1027, 2005. 25. Huang AJ, and Tseng SC. Corneal epithelial wound healing in the absence of limbal epithelium. Invest Ophthalmol Vis Sci 32: 96-105, 1991. 26. Huang AJ, Watson BD, Hernandez E, and Tseng SC. Induction of conjunctival transdifferentiation on vascularized corneas by photothrombotic occlusion of corneal neovascularization. Ophthalmology 95: 228-235, 1988. 27. Ignoffo RJ. Overview of bevacizumab: a new cancer therapeutic strategy targeting vascular endothelial growth factor. Am J Health Syst Pharm 61: S21-26, 2004. 28. Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, and Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol 141: 267-275, 2006. 29. Jaworski CJ, Aryankalayil-John M, Campos MM, Fariss RN, Rowsey J, Agarwalla N, Reid TW, Dushku N, Cox CA, Carper D, and Wistow G. Expression analysis of human pterygium shows a predominance of conjunctival and limbal markers and genes associated with cell migration. Mol Vis 15: 2421-2434, 2009. 30. Joussen AM, Poulaki V, Mitsiades N, Stechschulte SU, Kirchhof B, Dartt DA, Fong GH, Rudge J, Wiegand SJ, Yancopoulos GD, and Adamis AP. VEGF-dependent conjunctivalization of the corneal surface. Invest Ophthalmol Vis Sci 44: 117-123, 2003. 31. Jumblatt MM, McKenzie RW, and Jumblatt JE. MUC5AC mucin is a component of the human precorneal tear film. Invest Ophthalmol Vis Sci 40: 43-49, 1999. 32. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, and Bergsland E. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21: 60-65, 2003. 33. Kaye S, and Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res 25: 355-380, 2006. 34. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, and Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844, 1993. 35. Kim SW, Ha BJ, Kim EK, Tchah H, and Kim TI. The effect of topical bevacizumab on corneal neovascularization. Ophthalmology 115: e33-38, 2008. 36. Kim TI, Chung JL, Hong JP, Min K, Seo KY, and Kim EK. Bevacizumab application delays epithelial healing in rabbit cornea. Invest Ophthalmol Vis Sci 50: 4653-4659, 2009. 37. Kim TI, Kim SW, Kim S, Kim T, and Kim EK. Inhibition of experimental corneal neovascularization by using subconjunctival injection of bevacizumab (Avastin). Cornea 27: 349-352, 2008. 38. Koenig Y, Bock F, Horn F, Kruse F, Straub K, and Cursiefen C. Short- and long-term safety profile and efficacy of topical bevacizumab (Avastin) eye drops against corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 247: 1375-1382, 2009. 39. Kruse FE, Chen JJ, Tsai RJ, and Tseng SC. Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium. Invest Ophthalmol Vis Sci 31: 1903-1913, 1990. 40. Kurpakus MA, Stock EL, and Jones JC. Expression of the 55-kD/64-kD corneal keratins in ocular surface epithelium. Invest Ophthalmol Vis Sci 31: 448-456, 1990. 41. Lassota N. Clinical and histological aspects of CNV formation: studies in an animal model. Acta Ophthalmol 86 Thesis 2: 1-24, 2008. 42. Lee SH, Leem HS, Jeong SM, and Lee K. Bevacizumab accelerates corneal wound healing by inhibiting TGF-beta2 expression in alkali-burned mouse cornea. BMB Rep 42: 800-805, 2009. 43. Levy J, Benharroch D, and Lifshitz T. Bilateral severe progressive idiopathic lipid keratopathy. Int Ophthalmol 26: 181-184, 2005. 44. Li W, Hayashida Y, Chen YT, and Tseng SC. Niche regulation of corneal epithelial stem cells at the limbus. Cell Res 17: 26-36, 2007. 45. Lim P, Fuchsluger TA, and Jurkunas UV. Limbal stem cell deficiency and corneal neovascularization. Semin Ophthalmol 24: 139-148, 2009. 46. Lin YS, Nguyen C, Mendoza JL, Escandon E, Fei D, Meng YG, and Modi NB. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J Pharmacol Exp Ther 288: 371-378, 1999. 47. Ma DH, Chen JK, Zhang F, Lin KY, Yao JY, and Yu JS. Regulation of corneal angiogenesis in limbal stem cell deficiency. Prog Retin Eye Res 25: 563-590, 2006. 48. Maggs DJ. Cornea and Sclera. In: Maggs DJ, Miller PE, Ofri R, and Slatter DH, ed. Slatter's fundamentals of veterinary ophthalmology. Saunders Elsevier, St. Louis, Mo., 2008. 49. Manzano RP, Peyman GA, Khan P, Carvounis PE, Kivilcim M, Ren M, Lake JC, and Chevez-Barrios P. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol 91: 804-807, 2007. 50. Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, and Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology 112: 1035-1047, 2005. 51. Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, and Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol 88: 1280-1284, 2004. 52. Nakamura T, and Kinoshita S. Ocular surface reconstruction using cultivated mucosal epithelial stem cells. Cornea 22: S75-80, 2003. 53. Nasisse MP, Guy JS, Davidson MG, Sussman WA, and Fairley NM. Experimental ocular herpesvirus infection in the cat. Sites of virus replication, clinical features and effects of corticosteroid administration. Invest Ophthalmol Vis Sci 30: 1758-1768, 1989. 54. Oh JY, Kim MK, and Wee WR. Subconjunctival and intracorneal bevacizumab injection for corneal neovascularization in lipid keratopathy. Cornea 28: 1070-1073, 2009. 55. Philipp W, Speicher L, and Humpel C. Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci 41: 2514-2522, 2000. 56. Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, and Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57: 4593-4599, 1997. 57. Rosenfeld PJ, Fung AE, and Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 36: 336-339, 2005. 58. Rosenstein JM, and Krum JM. New roles for VEGF in nervous tissue--beyond blood vessels. Exp Neurol 187: 246-253, 2004. 59. Sacchetti M, Lambiase A, Cortes M, Sgrulletta R, Bonini S, and Merlo D. Clinical and cytological findings in limbal stem cell deficiency. Graefes Arch Clin Exp Ophthalmol 243: 870-876, 2005. 60. Sonoda KH, Nakao S, Nakamura T, Oshima T, Qiao H, Hisatomi T, Kinoshita S, and Ishibashi T. Cellular events in the normal and inflamed cornea. Cornea 24: S50-S54, 2005. 61. Sridhar MS, Vemuganti GK, Bansal AK, and Rao GN. Impression cytology-proven corneal stem cell deficiency in patients after surgeries involving the limbus. Cornea 20: 145-148, 2001. 62. Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, and Kalluri R. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 278: 12605-12608, 2003. 63. Tsai RJ, Sun TT, and Tseng SC. Comparison of limbal and conjunctival autograft transplantation in corneal surface reconstruction in rabbits. Ophthalmology 97: 446-455, 1990. 64. Tseng SC. Concept and application of limbal stem cells. Eye 3: 141-157, 1989. 65. Tseng SC, Espana EM, Kawakita T, Di Pascuale MA, Li W, He H, Liu TS, Cho TH, Gao YY, Yeh LK, and Liu CY. How does amniotic membrane work? Ocul Surf 2: 177-187, 2004. 66. Tseng SC, Prabhasawat P, Barton K, Gray T, and Meller D. Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol 116: 431-441, 1998. 67. Turner HC, Budak MT, Akinci MA, and Wolosin JM. Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays. Invest Ophthalmol Vis Sci 48: 2050-2061, 2007. 68. Yoeruek E, Ziemssen F, Henke-Fahle S, Tatar O, Tura A, Grisanti S, Bartz-Schmidt KU, and Szurman P. Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn. Acta Ophthalmol 86: 322-328, 2008. 69. Zachary I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol 280: C1375-1386, 2001. 70. Zheng M, Deshpande S, Lee S, Ferrara N, and Rouse BT. Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis. J Virol 75: 9828-9835, 2001. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46828 | - |
dc.description.abstract | 眼角膜位於視軸最外層,平時藉由血管新生因子與抗血管新生因子之間的恆定、以及眼輪部幹細胞所形成的障壁,維持角膜無血管的透光狀態。若發生角膜輪狀部幹細胞缺損(limbal stem cell deficiency;LSCD),發炎反應以及角結膜障壁之缺乏,會激活眼角膜生成新生血管、角膜結膜化,過多的新生血管更可能加劇發炎反應,最終眼角膜會因上述的症狀失去透光度進而影響視力。在所有調控血管生成的機制中,血管內皮生長因子(vascular endothelium growth factor;VEGF) 扮演了重要角色。近年來許多研究將抗血管內皮生長因子 (anti-VEGF) 藥物用來對抗腫瘤的機制套用在眼部新生血管之病變上,不管是在實驗動物模式或是人類臨床試驗,都發現抗血管內皮生長因子藥物bevacizumab (Avastin®;癌思停),能成功地抑制角膜新生血管。本實驗利用眼輪部缺損的實驗兔模式,以結膜下腔注射的給藥途徑,評估bevacizumab在早期、中期與晚期之不同起始治療時間下,對於角膜新生血管與角膜結膜化的抑制效果。結果,無論是巨觀利用影像記錄與量化分析血管生長與角膜混濁的程度,抑或微觀使用免疫組織化學染色調查角膜上細胞性狀表現,皆發現早期使用bevacizumab能較有效地控制角膜新生血管與結膜化,並且得知bevacizumab具有時間依賴性的治療特點。僅管如此,其他更貼近臨床病症的實驗模式以及用於臨床的治療劑量在未來仍有待進一步研究。 | zh_TW |
dc.description.abstract | The cornea locates on the outer structure of optic axis. The transparency of cornea that is angiogenic privilege relies on the regulation among antiangiogenic factors and angiogenic factors and the existence of limbal stem cells between cornea and conjunctiva. If limbal stem cell deficiency (LSCD) develops, corneal neovascularization and conjunctivalization may be manifested following inflammatory cascade, finally leading to decreased corneal transparency and vision. Vascular endothelium growth factor (VEGF) is well-known to play an important role in angiogenesis. The anti-VEGF drug, bevacizumab (Avastin®), which is an anti-cancer medicine was reported to be effective in treating corneal neovascularization in animal experiments and clinical trials recently. In this study, we utilzed a limbal insufficiency rabbit model and treated with different onset time of subconjunctival injection. To compare the inhibitory effect of the early, mid, and late treatment by bevacizumab on corneal pathological changes, the corneal neovascularization and conjunctivalization were grossly recorded and quantified with image analysis, and expression of corneal or conjunctival phenotype by the corneal surface cells was examined immunohistochemically. The most successful group in controlling corneal neovascularization and conjunctivalization was the early treatment group, and followed by the mid and late treatment group sequentially. Although we found that the therapeutic characteristics of bevacizumab was time-dependent, the simulation of real clinical condition such as the experimental model and the therapeutic dosage remains to be investigated in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:41:56Z (GMT). No. of bitstreams: 1 ntu-99-R97643008-1.pdf: 4143856 bytes, checksum: f4e0abbf06e9196dfc120c3dc156cd7c (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 致謝 ii
中文摘要 iii 英文摘要 iv 第一章 緒論 1 第一節 眼輪部幹細胞缺損與新生血管的生成 1 第二節 Bevacizumab (Avastin®) 2 第三節 研究目的 2 第二章 文獻探討 3 第一節 角膜輪狀部幹細胞缺損之病理機制 3 一、 角膜新生血管 3 二、 角膜結膜化 4 第二節 角膜輪狀部幹細胞缺損之治療 5 第三節 抗血管內皮生長因子藥物之標靶治療 6 一、 血管內皮生長因子 6 二、 抗血管內皮生長因子藥物 7 第四節 抗血管內皮生長因子藥物治療角膜新生血管的臨床運用和動物實驗 9 第五節 抗血管內皮生長因子藥物對於角膜毒性之探討 10 第三章 實驗材料與方法 12 第一節 實驗材料 12 第二節 實驗方法 12 一、 眼輪狀部幹細胞缺損之實驗兔模式 12 二、 藥物注射方式 (早期、中期、晚期) 13 三、 角膜新生血管與結膜化之紀錄觀察 13 四、 組織病理學 14 五、 細胞群落分析 15 六、 統計分析方法 15 第四章 實驗結果 17 第一節 肉眼下之角膜表面變化 17 第二節 角膜新生血管之統計差異 17 第三節 角膜混濁度之統計差異 18 第四節 角膜結膜化之免疫組織化學染色 18 第五節 角膜上皮細胞群落分析 19 第五章 討論 21 第一節 以bevacizumab治療眼輪部幹細胞缺損引發角膜新生血管的抑制情形 21 第二節 以bevacizumab治療眼輪部幹細胞缺損引發角膜混濁的控制情形 22 第三節 以免疫組織化學染色評估不同起始治療時間下角膜結膜化之抑制情形 23 第四節 不同起始治療時間之探討 24 第五節 本研究之優點與缺點 26 第六節 未來展望 27 第六章 結論 29 參考文獻 30 圖目錄 36 表目錄 37 | |
dc.language.iso | zh-TW | |
dc.title | Bevacizumab結膜下腔注射在眼輪部幹細胞缺損模式中對於角膜新生血管與角膜結膜化的抑制效果 | zh_TW |
dc.title | Inhibitory Effect of Bevacizumab on Corneal Neovascularization and Corneal Conjunctivalization in the Limbal Stem Cell Deficiency Model | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 陳偉勵(Wei-Li Chen) | |
dc.contributor.oralexamcommittee | 葉力森,詹東榮,劉振軒 | |
dc.subject.keyword | 角膜新生血管,角膜結膜化,輪狀部幹細胞缺損,癌思停,時間依賴性, | zh_TW |
dc.subject.keyword | corneal neovascularization,corneal conjunctivalization,limbal stem cell deficiency (LSCD),bevacizumab,time-dependent, | en |
dc.relation.page | 51 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-23 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床動物醫學研究所 | zh_TW |
顯示於系所單位: | 臨床動物醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-99-1.pdf 目前未授權公開取用 | 4.05 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。