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

Inhibitory Effect of Bevacizumab on Corneal Neovascularization and Corneal Conjunctivalization in the Limbal Stem Cell Deficiency Model

郭廣慈(Kuang-Tzu Kuo)

指導教授 ： 林中天

共同指導教授 ： 陳偉勵(Wei-Li Chen)

國立臺灣大學/獸醫專業學院/臨床動物醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.00657

摘要

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。

關鍵字

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

並列摘要

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.

並列關鍵字

corneal neovascularization ； corneal conjunctivalization ； limbal stem cell deficiency (LSCD) ； bevacizumab ； time-dependent

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