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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊台鴻(Tai-Horng Young) | |
| dc.contributor.author | Po-Chun Wang | en |
| dc.contributor.author | 王柏鈞 | zh_TW |
| dc.date.accessioned | 2021-06-16T13:10:58Z | - |
| dc.date.available | 2020-07-20 | |
| dc.date.copyright | 2020-07-20 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-08 | |
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Safety evaluation of alpha-lipoic acid (ALA). Regul Toxicol Pharmacol. 2006;46: 29–41. [44] Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2011;51:993–999. [45] Hiltunen JK, Schonauer MS, Autio KJ, Mittelmeier TM, Kastaniotis AJ, Dieckmann CL. Mitochondrial fatty acidsynthesis type ii: more than just fatty acids. J Biol Chem. 2009; 284:9011–9015. [46] Morikawa T, Yasuno R, Wada H. Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria. FEBS Lett. 2001;498:16–21. [47] Fujiwara K, Takeuchi S, Okamura-Ikeda K, Motokawa Y. Purification, characterization, and cDNA cloning of lipoate activating enzyme from bovine liver. J Biol Chem. 2001;276: 28819–28823. [48] Jordan SW, Cronan JE. A new metabolic link. 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Experimental validation of acoustic radiation force induced shear wave interference patterns. Phys Med Biol. 2012; 57: 21–30. [54] Xinyu Zhang et al. Noninvasive assessment of age‑related stiffness of crystalline lenses in a rabbit model using ultrasound elastography. BioMed Eng OnLine (2018) 17:75. https://doi.org/10.1186/s12938-018-0509-1 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61727 | - |
| dc.description.abstract | 老花眼為退化性的屈光疾患，致中老年人無法有良好的調視能力，尤其無法使水晶體維持其聚焦的功能，妨礙近距離閱讀的視力。在現今高/老齡化社會與慢性疾病盛行率逐漸攀升的發展中與已開發國家，甚或在全球資源分配不均，資源匱乏的第三世界國家，相關藥物治療發展有其在預防與老人醫學的角色。
由於參酌過去學者對於老花眼、白內障的發展有水晶體失能症候群 (dysfunctional lens syndrome) 的說法，本研究沿用過去人眼水晶體表皮細胞株 (Human lens epithelial cell-B3, HLE-B3) 的後囊性白內障研究模型，以轉化生長因子-β [Transforming Growth Factor-β (TGF-β)] 細胞因子(cytokines)為表皮間質化 (Epithelial-Mesenchymal Transition, EMT) 的誘導因子。另外，受測開發中藥物的選擇以機制相仿的兩種藥物，首以2019年4-12月進入二期臨床試驗用藥的硫辛酸 (alpha-lipoic acid) 為主軸，乙醯半胱氨酸 (N-Acetylcysteine) 為輔，因兩者均有使細胞生長於穀胱甘肽 (GSH) 增加之環境，抑制晶體表皮細胞間質化與減緩水晶體失能發展之機制。 本研究以細胞(in vitro)及器官(ex vivo)兩層面探討藥物作用；細胞層級上，在TGF-β濃度為2 ng/ml時，硫辛酸較乙醯半胱氨酸能抑制表皮間質化的波形蛋白(vimentin) 螢光染色表現。器官層級上，本研究參酌過去學者嘗試以超音波－剪力波彈性造影量測不同年紀兔眼水晶體彈性度，測試發現硫辛酸亦較乙醯半胱氨酸能抑制TGF-β誘導水晶體退化模型。藥物水/脂溶性與帶電性可為影響藥效的因素，未來研究可考慮進一步接枝/包覆等增加正電性、脂溶性，以增加細胞膜與角膜穿透度等。期望未來本研究測試藥物的方法可資日後老花眼藥物發展的基石，能為第三世界國家提供替代/預防性醫療，並對於預防醫學與老人醫學有些許貢獻。 | zh_TW |
| dc.description.abstract | Presbyopia is a degenerative disorder that hinders accommodation, which compromises near vision. In recent aging/aged society, increasing chronic medical conditions, and third-world countries where lack of medical resource, presbyopia medication development has its role in preventive and geriatric medicine.
According to previous studies, dysfunctional lens syndrome contains the spectrum of presbyopia and cataract, therefore, our study followed posterior capsular opacity (cataract) model which cytokine TGF-β induces epithelial-mesenchymal transition. The developing medications tested in our study involves alpha-lipoic acid (which had entered stage 2 clinical trial on April through December 2019) and N-Acetylcysteine. Both of their mechanism increases Glutathione (GSH) in cellular micro-environment, therefore, which suppresses epithelial-mesenchymal transition and slower the development of dysfunctional lens syndrome. The in vitro study presented that HLE-B3 cell line under 2 ng/ml TGF-β, initially treated alpha lipoic acid suppressed vimentin immunofluorescence expression better than N-Acetylcysteine. In ex-vivo porcine lens organ culture, we reviewed previous studies used ultrasound shear-wave elastography for evaluation of lens elasticity in rabbits’ eyes at different ages, and ocular medication (pilocarpine and atropine) effect on ocular tissues. We had found alpha-lipoic acid suppresses TGF-β induced lens stiffness (which is correlated with group velocity) better than N-acetylcysteine. Medication hydrophilicity may be the factor hinders effectiveness, further studies on chemical grafting and encapsulating for increasing drug positivity, lipophilicity may achieve better membrane and corneal permeability. We hope the drug testing methods this study presented would trigger further presbyopia drug development, which may provide preventive measures/ alternative medical treatment for third world countries, and further contributes to preventive and geriatric medicine. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T13:10:58Z (GMT). No. of bitstreams: 1 U0001-2206202015273400.pdf: 4306798 bytes, checksum: c85966a3034c557b4cb8d04c9cc20226 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員會審定書 # 誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS iv LIST OF FIGURES vi LIST OF TABLES vii Chapter 1 Introduction 1 1.1 Presbyopia 1 1.2 Lenticular structures 5 1.3 Lens Epithelial Cell with Epithelial-Mesenchymal Transition 8 1.4 Current Medical Treatment on Presbyopia and Development 12 1.5 Ultrasound Elastography Measurement for Lens Elasticity 14 Chapter 2 Materials and Methods 17 2.1 Materials 17 2.2 Methods 19 2.2.1 Human Lens Epithelial Cell Line (HLE-B3) Culture 19 2.2.2 Alamar Blue Assay (Cell Viability Test) 20 2.2.3 Immunofluorescence 20 2.2.4 Porcine Lens ex vivo Culture 22 2.2.5 Ultrasound Shear-wave Elastography on Porcine Lens Elasticity 22 2.2.6 Statistical Analysis 23 Chapter 3 Results 24 3.1 HLE-B3 Culture Medication Treatment Cell Viability 24 3.2 Immunofluorescence 24 3.3 Porcine Lens ex vivo Organ Culture Degenerative Model Establishment 25 3.4 Porcine Lens ex vivo Organ Culture Degenerative Model Under Treatment 26 Chapter 4 Discussion 27 Chapter 5 Conclusion and Perspective 32 Figures and Tables 33 References 46 | |
| dc.language.iso | en | |
| dc.subject | 乙醯半胱氨酸 | zh_TW |
| dc.subject | 硫辛酸 | zh_TW |
| dc.subject | 轉化生長因子-β | zh_TW |
| dc.subject | 超音波－剪力波彈性造影 | zh_TW |
| dc.subject | 人眼水晶體表皮細胞株B3 | zh_TW |
| dc.subject | 水晶體失能症候群 | zh_TW |
| dc.subject | 老花眼 | zh_TW |
| dc.subject | 表皮間質化 | zh_TW |
| dc.subject | N-Acetylcysteine | en |
| dc.subject | Dysfunctional lens syndrome | en |
| dc.subject | Human lens epithelial cell-B3 | en |
| dc.subject | Epithelial-mesenchymal transition | en |
| dc.subject | Transforming growth factor-β | en |
| dc.subject | Alpha lipoic acid | en |
| dc.subject | Presbyopia | en |
| dc.subject | Ultrasound shear-wave elastography | en |
| dc.title | 開發中老花眼藥物對於晶體表皮細胞間質化與晶體彈性度影響之探討 | zh_TW |
| dc.title | Comparison of Current Developing Medication on Suppression of Presbyopia Development－Lens Epithelial Cell Epithelial-Mesenchymal Transition and Lens Capsular Elasticity | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.author-orcid | 0000-0002-1847-3581 | |
| dc.contributor.advisor-orcid | 楊台鴻(0000-0001-5338-4747) | |
| dc.contributor.oralexamcommittee | 王一中(I-Jong Wang),蔡景耀(Ching-Yao Tsai) | |
| dc.contributor.oralexamcommittee-orcid | 王一中(0000-0002-3045-0614) | |
| dc.subject.keyword | 老花眼,水晶體失能症候群,人眼水晶體表皮細胞株B3,表皮間質化,轉化生長因子-β,硫辛酸,乙醯半胱氨酸,超音波－剪力波彈性造影, | zh_TW |
| dc.subject.keyword | Presbyopia,Dysfunctional lens syndrome,Human lens epithelial cell-B3,Epithelial-mesenchymal transition,Transforming growth factor-β,Alpha lipoic acid,N-Acetylcysteine,Ultrasound shear-wave elastography, | en |
| dc.relation.page | 52 | |
| dc.identifier.doi | 10.6342/NTU202001102 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-07-08 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
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