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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 錢宗良(Chung-Liang Chien) | |
dc.contributor.author | Nan-Kai Wang | en |
dc.contributor.author | 王南凱 | zh_TW |
dc.date.accessioned | 2021-05-16T16:20:47Z | - |
dc.date.available | 2013-09-24 | |
dc.date.available | 2021-05-16T16:20:47Z | - |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-02 | |
dc.identifier.citation | Akhmedov NB, Piriev NI, Chang B, et al. (2000): A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proc Natl Acad Sci U S A 97: 5551-5556.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6094 | - |
dc.description.abstract | Goldmann-Favre徵候症,也稱為增強型 S-圓錐 (enhanced S-cone) 徵候症,是一個遺傳性視網膜退化疾病,這個退化疾病主要是由感光細胞增加所導致視網膜發育不良和變性。我們先前已經證明在rd7小鼠(enhanced S-cone徵候症小鼠模式)視網膜中自發性螢光(AF)點是來自於微膠細胞,而不是視網膜色素上皮 (RPE) 細胞,這些微膠細胞呈現 F4/80陽性。大多數微膠細胞出現在視網膜皺褶內(retinal rosette),推測這些微膠細胞的出現是幫助視網膜色素上皮細胞吞噬在視網膜皺褶內部分非接觸的感光細胞外節(outer segment) 的碎片。雖然微膠細胞被認為參與許多神經退化性疾病,然而微膠細胞和導致視網膜退化之間的關係是未知的。
在此次研究中,連續分析視網膜皺褶及視網膜自發性螢光點,我們發現視網膜皺褶出現時間點較自發性螢光點早,這表示微膠細胞是在外核層折疊後被招募來的。我們推測微膠細胞在初期是扮演幫忙的角色,主要是在維護感光細胞和視網膜色素上皮細胞之間的環境並清理感光細胞外節的碎片。 利用轉殖基因小鼠(Mafia)的優勢,我們藉由二代交叉繁殖成功配種出rd7/rd7;Tg/Tg小鼠。這種小鼠體內的微膠細胞帶都表現綠色螢光及自殺基因,它可以藉由AP20187(FA506 dimerizer的)引發Fas所導致的的細胞凋亡。我們發現這些80%綠色螢光細胞同時表現Iba-1 (常駐微膠細胞標記)。我們發現在剔除全身血液循環中的微膠細胞後,視網膜中仍然可以偵測到綠色螢光細胞,依此推測AP20187無法通過血液-視網膜屏障;所以只有血液循環中的微膠細胞可以被殺死。我們更發現在剔除全身血液循環中的微膠細胞後,小鼠呈現後期視網膜退化的徵兆。 視網膜中自發性螢光(AF)點的增加和常駐微膠細胞的複製增生有關。常駐微膠細胞的複製增生伴隨著發炎細胞因子(cytokine)的表達增加(如IL-1β, IL-6, and TNF-α)。這種發炎細胞因子的增加可能加速視網膜變性。這項研究不只確定發炎在視網膜退化中發病機制的角色,也可以利用參與其中的細胞因子作為今後治療視網膜退化的方向。 | zh_TW |
dc.description.abstract | Goldmann-Favre Syndrome, also known as enhanced S-cone syndrome, is an inherited retinal degeneration in which a gain of photoreceptor cell types results in retinal dysplasia and degeneration. We demonstrated previously that microglia that are stained positively for F4/80, rather than retinal pigment epithelium (RPE) cells, may contribute to the hyper-autofluorescent (AF) spots observed in the retina of rd7 mice, which are a mouse model of enhanced S-cone syndrome (ESCS). Most of these cells were present inside retinal rosettes and presumably help RPE cells to phagocytose the noncontact outer segment debris located within the rosettes. Although microglia have been implicated in the pathogenesis of many neurodegenerative diseases, the fundamental role of these cells in this disease is unknown.
In the current study, sequential analyses suggest that microglia are recruited and appear after outer nuclear layer folding. Using mice with the macrophage Fas-induced apoptosis (Mafia) transgene, we generated double-mutant mice and studied the role of the resident retinal microglia. Microglial cells in these double-mutant mice express enhanced green fluorescent protein (EGFP) and a suicide gene, which can trigger Fas-medicated apoptosis via systemic treatment with AP20187 (FA506 dimerizer). We demonstrated that more than 80% of the EGFP+ cells in rd7/rd7;Tg/Tg mice retina expressed Iba-1, which is a resident microglia marker. We found resident microglia are still present in the retina after applying AP20187 because AP20187 does not cross the blood-retina barrier. Hence, only circulating bone marrow (BM)-derived microglia are depleted. In addition, depletion of circulating BM-derived microglia accelerates retinal degeneration in rd7 mice. An increased number of autofluorescent (AF) spots are a consequence of resident microglia proliferation which in turn establishes an inflammatory cytokine milieu via the upregulation of IL-1β, IL-6, and TNF-α expression. This inflammation likely accelerates retinal degeneration. This study has identified not only inflammation as a critical step in the pathogenesis of retinal degeneration, but also the involvement of specific cytokine genes that could serve as future treatment targets in retinal degenerations. | en |
dc.description.provenance | Made available in DSpace on 2021-05-16T16:20:47Z (GMT). No. of bitstreams: 1 ntu-102-D95446004-1.pdf: 12659992 bytes, checksum: 639e76801f8cb9d0ec99c526dd635ee1 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | Acknowledgement----------------------------------------------------------------- i
Abbreviation ---------------------------------------------------------------------- v Summary of Dissertation in Chinese ------------------------------------------- 1 Summary of Dissertation in English ------------------------------------------- 3 Chapter I. General Introduction ------------------------------------------------- 5 Enhanced S-Cone Syndrome ------------------------------------------------- 6 Retinal Degeneration 7 (rd7) Mice ------------------------------------------ 6 Retinal Pigment Epithelium and Photoreceptor ---------------------------- 8 Autofluorescent Spot in Retina ---------------------------------------------- 8 Microglia in Retinal Degeneration ------------------------------------------ 9 Transgenic Mice for Macrophage Fas-Induced Apoptosis (Mafia) ---- 10 Specific Aims of Current Study --------------------------------------------- 11 Figure legends and Figures -------------------------------------------------- 15 Chapter II. Cellular Origin of Fundus Autofluorescence in Patients and Mice with Defective NR2E3 Gene -------------------------------------- 17 Abstract ------------------------------------------------------------------------ 18 Introduction ------------------------------------------------------------------- 19 Materials and Methods ------------------------------------------------------- 21 Results ------------------------------------------------------------------------- 25 Discussion --------------------------------------------------------------------- 29 Figure legends and Figures -------------------------------------------------- 34 Chapter III. Origin of Fundus Hyperautofluorescent Spots, and Their Role in Retinal Degeneration in a Mouse Model of Goldmann-Favre Syndrome ------------------------------------------------------------------------- 46 Abstract ------------------------------------------------------------------------ 47 Introduction -------------------------------------------------------------------- 49 Materials and Methods ------------------------------------------------------- 52 Results -------------------------------------------------------------------------- 60 Discussion --------------------------------------------------------------------- 67 Figure legends and Figures -------------------------------------------------- 75 Chapter IV. Conclusion and Future Prospective ------------------------- 93 Bibliography --------------------------------------------------------------------- 97 Appendix------------------------------------------------------------------------- 104 | |
dc.language.iso | en | |
dc.title | 微膠細胞在NR2E3基因缺陷小鼠視網膜退化扮演角色之探討 | zh_TW |
dc.title | The Role of Microglia in Retinal Degeneration of Mice with Defective NR2E3 Gene | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 盧國賢(Kuo-Shyan Lu),呂俊宏(June-Horng Lue),賴旗俊(Chi-Chun Lai),楊長豪(Chang-Hao Yang) | |
dc.subject.keyword | 視網膜退化,微膠細胞,自發性螢光,轉殖基因小鼠, | zh_TW |
dc.subject.keyword | retinal degeneration,microglia,autofluorescence,transgenic mice, | en |
dc.relation.page | 104 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2013-08-02 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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