- 學位論文
建立及分析角膜新生血管相關脂肪性角膜病變之紐西蘭白兔動物模式
Establishment and Characterization of a Rabbit Model of Corneal Neovascularization with Lipid Keratopathy
摘要
脂肪性角膜病變為描述角膜因血管新生而繼發脂肪沈積的專有名詞，此疾病會嚴重影響眼睛的美觀以及視力。本研究之主要目的為建立脂肪性角膜病變之紐西蘭白兔動物模式，次要目的為藉此動物模式在結膜下注射能直接阻抗血管內皮生長因子的人類化單株抗體藥物bevacizumab (Avastin®；癌思停)，評估此藥物對於角膜新生血管和脂肪沈積的抑制效果。在脂肪性角膜病變動物模式的建立上，會藉由合併角膜新生血管動物模式以及高血脂動物膜者兩者來達成，又依此兩者的先後順序不同分為兩組，第一組先誘導角膜新生血管模式後，再誘導高血脂模式，第二組則先誘導高血脂模式後，再誘導角膜新生血管模式。兩組結果皆可見所有角膜出現明顯的晶體物質沈積，隨後進行活體共軛焦雷射掃描顯微鏡檢查、眼前段光學同調斷層掃描術檢查，以及製作成冷凍切片並使用油紅染色，證實角膜前基質的晶體沈積物質為脂肪，而且主要沈積部位為角膜前基質，因此成功地建立兩組脂肪性角膜病變動物模式。使用此兩組動物模式評估每週結膜下注射bevacizumab藥物5 mg之處置效果，另外評估連續10週注射藥物之副作用。兩組動物模式的所有藥物處置組別，皆沒有看到明顯的改善效果。本研究結果顯示成熟的脂肪性角膜病變對於藥物的反應不佳，另外在短期10週內使用高劑量的bevacizumab皆沒有明顯的副作用發生，未來可再評估更為早期的處置對於此疾病的抑制效果，以及更為長期的藥物副作用評估。本研究提供了一個良好且穩定的脂肪性角膜病變動物模式，提供了其他學者對於該疾病的控制及治療上能夠有更多的研究機會。
並列摘要
Lipid keratopathy is the term to describe lipid deposition in the cornea secondary to corneal neovascularization (NV). The disease causes the cosmetic problem, alters visual acuity and worsens the prognosis of corneal surgery. The primary purpose of this study is to establish a rabbit animal model of lipid keratopathy, and then the secondary purpose is to evaluate the inhibitory effects on corneal NV and lipid deposition by subconjunctival injection of bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor. Both animal models of corneal NV and hyperlipidemia were combined for establishing the animal model of lipid keratopathy, and the lipid keratopathy model was divided into two groups. The corneal NV model was induced before the hyperlipidemia model in the first group, and the second one was opposite in order. Significant crystal depositions were noted in all corneas of two groups. The treated eyes were examined with in vivo confocal laser-scanning microscopy and anterior segment optical coherence tomography, and they were prepared for corneal cryosections stained with Oil red O stain. The crystal depositions located in the anterior corneal stroma were confirmed for lipid. Therefore, the two rabbit models of lipid keratopathy were established successfully. Each of two lipid keratopathy models was used to evaluate the therapeutic effects by subconjunctival injection of 5 mg bevacizumab weekly and the side effects of bevacizumab by injecting for 10 weeks. There were no improvement noted obviously in all drug management groups of two lipid keratopathy models. The response to the drug was not significant in the eye with advanced lesion of lipid keratopathy, and there were no obvious side effects after injecting high dose of bevacizumab for 10 weeks. The inhibitory effects of early management on lipid keratopathy and the side effects of long-term injecting bevacizumab remain to investigate further in the future. The good animal model of lipid keratopathy was established stably and successfully in this study. The animal model will be useful in studies toward the developing new methods for controlling and treating lipid keratopathy.
參考文獻
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