本研究之目的是分析與比較不同光照環境下，魚類眼球水晶體蛋白質表現的多樣性。我們利用最先進的蛋白質組學的方法，來觀察眼球水晶體蛋白質的變化，特別是生活於永久黑暗環境下的魚類，其眼球水晶體功能的喪失與演化的相關性。
實驗主題分為三部份：（1）以夜行性退化眼球的黃鱔和土虱，與晝行性眼球正常的斑馬魚作比較，來探究各種水晶體蛋白在光照視覺上的重要性。（2）分析比較側斑兵鯰的白化個體 (Corydoras aeneus var.)與正常個體(Corydoras aeneus)，眼球水晶體蛋白表現之異同。（3）比較由淺海至深海環境下生存的10個海水魚種，其眼球水晶體蛋白質的組成分佈。
研磨萃出魚類眼球水晶體的可溶性總蛋白後，將蛋白質經由一維和二維電泳凝膠 (1-D or 2-D gel) 的分離，及新型的散彈分析法，而一維和二維的蛋白條帶或斑點，經酵素水解後以LC-MS/MS液相色層串聯質譜法，憑藉資料庫中斑馬魚的蛋白質體為比對標準，進行分析。研究結果，大致可知魚類的晶狀體蛋白質，主要包括α-、β-和γ-晶狀體蛋白質。
在黃鱔的眼球水晶體中，β-和γ-晶狀體蛋白質含量約超過總體蛋白質的98%，而幾乎沒有α-晶狀體蛋白質被檢測出來。而儘管夜行性黃鱔與土虱的生活習性相近，但在α-晶狀體蛋白質的表現上有明顯的不同。
有關比較側斑兵鯰 (Corydoras aeneus) 與該種之白化個體 (Corydoras aeneus var.) 的結果，其各晶狀體蛋白質的百分率組成均很相近。然而在2-D凝膠上，α-晶狀體表現區，在側斑兵鯰原生個體的3個點的分佈明顯不同於白化個體的6個點的表現。
有關生活在淺海層，中深層與深海層的魚種，其眼球水晶體蛋白質的比較中，顯示隨著海水深度的增加，α-晶狀體的百分率逐漸減少，而γ-晶狀體的組成百分率，卻逐漸增加。
利用蛋白質體學的方法研究魚種中的α-，β-和γ-晶狀體蛋白，能清楚地表明魚類之相同蛋白質的多樣性和複雜性。值得注意的是，在夜行性退化眼球的黃鱔與深海底棲性的黑口鮟鱇(Lophiomus setigerus)中，其α-晶體蛋白質的減少，指出α-晶體蛋白質在魚類眼球水晶體中扮演保護的角色，可防止其它蛋白質的聚集現象，以維持不同環境下，脊椎動物眼球水晶體的透光度，是不可少的。而α-晶體蛋白質的伴護功能是未來值得更進一步研究的課題。

The aim of this study was to determine the lens crystallin diversity of fishes living in varied environmental habitats under different light conditions. We employed state-of-the-art proteomics methodologies to investigate proteomic change associated with the evolution of fish lenses particularly concerning the functional loss of lenses in eyes of fishes living under an environment of perpetual darkness.
The experiments were divided into three parts: the first part is to analyze the degenerative eye lenses of nocturnal rice eel and catfish as compared to diurnal zebrafish; the second part is to analyze and compare the different electrophoretic protein spots of albino-type fish (Corydoras aeneus var.) and wild-type fish (Corydoras aeneus); the third part is to analyze the crystallin distribution in the eye lenses of ten piscine species from epipelagic to bathypelagic environments.
Fish lenses were collected and homogenized to extract total soluble proteins. The protein mixtures were separated by one- and two-dimensional gel electrophoresis (1-D or 2-D gel), samples of the first-part study were analyzed by the newer gel-free shotgun proteomic strategy, followed by in-gel digestion and the digested protein bands or spots subjected to liquid chromatography coupled with tandem mass spectrometry. The proteomics data were analyzed and compared based on the proteomics databank of zebrafish. The validation and comparison of various crystallin families, e.g., α-, β-, and γ-crystallins were based on 1-D and 2-D sodium dodecyl sulfate–polyacrylamide gel electrophoresis.
In rice eel’s lenses, β- and γ-crystallins comprised more than 98% of total lens proteins whereas very little or almost no α-crystallin was detected. It was of interest to note that α-crystallin showing obvious differences in protein contents between the nocturnal fishes of rice eel and catfish in spite of the similarity in their living habitat.
For the wild type and albino mutant of Corydoras aeneus’s eye lenses, it was found that the crystallin content is very similar between the two. However the 2-D gel show that α-crystallin region of Corydoras aeneus lenses containing 3 protein spots, which was different from that of Corydoras aeneus var. lenses containing 6 spots.
For experiments on lens protein variation in fishes from environments of different light exposure such as fishes living in the epipelagic, mesopelagic and bathypelagic zones, the content of α-crystallin decreased, and γ-crystallin increased with the ocean depths of piscine living habitats.
The total numbers of α-, β-, and γ-crystallins in the piscine species examined by the current proteomics methodology clearly indicate the complexity and diversity of crystallin species present in different fish species. It is noteworthy that only small amount of α-crystallin was present in the degenerative eye lenses of rice eel and bathydemersal fish species (i.e., Lophiomus setigerus), which points to the fact that this crystallin acting as a chaperone protein may be essential in vertebrate species to protect lens proteins from aggregation and to maintain functional transparency of the lens under varied environmental conditions. A detailed study on the correlation between the chaperone function and lens development warrants future investigation.

論文審定書 …………………………………………………………… i
誌謝 …………………………………………………………… ii
摘要 …………………………………………………………… iii
英文摘要 …………………………………………………………… v
目錄 …………………………………………………………… vii

圖次 …………………………………………………………… ix
表次 …………………………………………………………… xi
第一章 研究背景與目的
第一節 視覺系統在生物演化的角色…………………………… 1
第二節 魚類視覺與其生存環境的相關性……………………… 1
第三節 水生魚類與陸生動物視覺上的不同…………………… 2
第四節 以蛋白質體 (proteome) 研究各種不同生活情況下之魚類水晶體…………………………………………………
2
第五節 研究的重點與目的……………………………………… 4
第二章 動物體眼球及水晶體之結構功能
第一節 水晶體的形成與構造…………………………………… 6
第二節 水晶體蛋白質 (crystallin) 的組成……………………… 7
第三節 水晶體蛋白各論………………………………………… 9
第三章 材料與方法
第一節 實驗材料………………………………………………… 19
第二節 實驗方法………………………………………………… 19
第四章 夜行性黃鱔及土虱與晝行性斑馬魚水晶體蛋白質體之特徵
第一節 摘要……………………………………………………… 27
第二節 前言……………………………………………………… 28
第三節 材料與方法……………………………………………… 29
第四節 結果與討論……………………………………………… 33
第五節 結論……………………………………………………… 41
第五章 白化症魚類眼球水晶體成分之特徵
第一節 摘要……………………………………………………… 43
第二節 前言……………………………………………………… 44
第三節 材料與方法……………………………………………… 45
第四節 結果……………………………………………………… 46
第五節 討論……………………………………………………… 47
第六節 結論……………………………………………………… 51
第六章 不同光強度海域魚類眼球水晶體蛋白質組成之差異
第一節 摘要……………………………………………………… 53
第二節 前言……………………………………………………… 54
第三節 材料與方法……………………………………………… 55
第四節 結果與討論……………………………………………… 56
第五節 結論……………………………………………………… 62
第七章 總結論…………………………………………………… 63
第八章 參考文獻………………………………………………… 145
附錄一 藥品配方與製作………………………………………… 160
附錄二 本論文研究期間發表之相關論文……………………… 164

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