請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58641
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 錢宗良(Chung-Liang Chien) | |
dc.contributor.author | I-Wen Huang | en |
dc.contributor.author | 黃依雯 | zh_TW |
dc.date.accessioned | 2021-06-16T08:23:32Z | - |
dc.date.available | 2014-02-25 | |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-01-23 | |
dc.identifier.citation | Airaksinen, M. S. and Saarma, M. (2002). The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci, 3, 383-394.
Airaksinen, M. S., Titievsky, A. and Saarma, M. (1999). GDNF family neurotrophic factor signaling: four masters, one servant? Mol Cell Neurosci, 13, 313-325. Arighi, E., Borrello, M. G. and Sariola, H. (2005). RET tyrosine kinase signaling in development and cancer. Cytokine & Growth Factor Reviews, 16, 441-467. Bassett, E. A., Korol, A., Deschamps, P. A., Buettner, R., Wallace, V. A., Williams, T. and West-Mays, J. A. (2012). Overlapping expression patterns and redundant roles for AP-2 transcription factors in the developing mammalian retina. Dev Dyn, 241, 814-829. Baudet, C., Pozas, E., Adameyko, I., Andersson, E., Ericson, J. and Ernfors, P. (2008). Retrograde signaling onto Ret during motor nerve terminal maturation. J Neurosci, 28, 963-975. Brantley, M. A., Jr., Jain, S., Barr, E. E., Johnson, E. M., Jr. and Milbrandt, J. (2008). Neurturin-mediated ret activation is required for retinal function. J Neurosci, 28, 4123-4135. Carniti, C., Belluco, S., Riccardi, E., Cranston, A. N., Mondellini, P., Ponder, B. A., Scanziani, E., Pierotti, M. A. and Bongarzone, I. (2006). The Ret(C620R) mutation affects renal and enteric development in a mouse model of Hirschsprung's disease. Am J Pathol, 168, 1262-1275. Chen, X., Nelson, C. D., Li, X., Winters, C. A., Azzam, R., Sousa, A. A., Leapman, R. D., Gainer, H., Sheng, M. and Reese, T. S. (2011). PSD-95 is required to sustain the molecular organization of the postsynaptic density. J Neurosci, 31, 6329-6338. Chien, C. L. and Liem, R. K. (1995). The neuronal intermediate filament, alpha-internexin is transiently expressed in amacrine cells in the developing mouse retina. Exp Eye Res, 61, 749-756. Clark, M. E. and Kraft, T. W. (2012). Measuring rodent electroretinograms to assess retinal function. Methods Mol Biol, 884, 265-276. Cuenca, N., Pinilla, I., Sauve, Y. and Lund, R. (2005). Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats. Eur J Neurosci, 22, 1057-1072. Demb, J. B. and Singer, J. H. (2012). Intrinsic properties and functional circuitry of the AII amacrine cell. Vis Neurosci, 29, 51-60. Dorval, K. M., Bobechko, B. P., Fujieda, H., Chen, S., Zack, D. J. and Bremner, R. (2006). CHX10 targets a subset of photoreceptor genes. J Biol Chem, 281, 744-751. Druillennec, S., Dorard, C. and Eychene, A. (2012). Alternative splicing in oncogenic kinases: from physiological functions to cancer. J Nucleic Acids, 2012, 639062. Fisher, S. K., Lewis, G. P., Linberg, K. A. and Verardo, M. R. (2005). Cellular remodeling in mammalian retina: results from studies of experimental retinal detachment. Prog Retin Eye Res, 24, 395-431. Fontana, X., Hristova, M., Da Costa, C., Patodia, S., Thei, L., Makwana, M., Spencer-Dene, B., Latouche, M., Mirsky, R., Jessen, K. R., Klein, R., Raivich, G. and Behrens, A. (2012). c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling. J Cell Biol, 198, 127-141. Frasson, M., Picaud, S., Leveillard, T., Simonutti, M., Mohand-Said, S., Dreyfus, H., Hicks, D. and Sabel, J. (1999). Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Invest Ophthalmol Vis Sci, 40, 2724-2734. Gargini, C., Terzibasi, E., Mazzoni, F. and Strettoi, E. (2007). Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol, 500, 222-238. Goetze, B., Schmidt, K. F., Lehmann, K., Altrock, W. D., Gundelfinger, E. D. and Lowel, S. (2010). Vision and visual cortical maps in mice with a photoreceptor synaptopathy: reduced but robust visual capabilities in the absence of synaptic ribbons. Neuroimage, 49, 1622-1631. Greferath, U., Grunert, U. and Wassle, H. (1990). Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. J Comp Neurol, 301, 433-442. Grondin, R. and Gash, D. M. (1998). Glial cell line-derived neurotrophic factor (GDNF): a drug candidate for the treatment of Parkinson's disease. J Neurol, 245, P35-42. Hammang, J. P., Behringer, R. R., Baetge, E. E., Palmiter, R. D., Brinster, R. L. and Messing, A. (1993). Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration. Neuron, 10, 1197-1209. Hansford, J. R. and Mulligan, L. M. (2000). Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis. J Med Genet, 37, 817-827. Hauck, S. M., Kinkl, N., Deeg, C. A., Swiatek-de Lange, M., Schoffmann, S. and Ueffing, M. (2006). GDNF family ligands trigger indirect neuroprotective signaling in retinal glial cells. Mol Cell Biol, 26, 2746-2757. Hayashi, H., Ichihara, M., Iwashita, T., Murakami, H., Shimono, Y., Kawai, K., Kurokawa, K., Murakumo, Y., Imai, T., Funahashi, H., Nakao, A. and Takahashi, M. (2000). Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor. Oncogene, 19, 4469-4475. Jain, S., Golden, J. P., Wozniak, D., Pehek, E., Johnson, E. M., Jr. and Milbrandt, J. (2006). RET is dispensable for maintenance of midbrain dopaminergic neurons in adult mice. J Neurosci, 26, 11230-11238. Jijiwa, M., Fukuda, T., Kawai, K., Nakamura, A., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M. (2004). A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia. Mol Cell Biol, 24, 8026-8036. Jomary, C., Darrow, R. M., Wong, P., Organisciak, D. T. and Jones, S. E. (2004). Expression of neurturin, glial cell line-derived neurotrophic factor, and their receptor components in light-induced retinal degeneration. Invest Ophthalmol Vis Sci, 45, 1240-1246. Jomary, C., Thomas, M., Grist, J., Milbrandt, J., Neal, M. J. and Jones, S. E. (1999). Expression patterns of neurturin and its receptor components in developing and degenerative mouse retina. Invest Ophthalmol Vis Sci, 40, 568-574. Jones, B. W., Kondo, M., Terasaki, H., Lin, Y., McCall, M. and Marc, R. E. (2012). Retinal remodeling. Jpn J Ophthalmol, 56, 289-306. Kaneda, M. (2013). Signal processing in the mammalian retina. J Nippon Med Sch, 80, 16-24. Keeley, P. W., Luna, G., Fariss, R. N., Skyles, K. A., Madsen, N. R., Raven, M. A., Poche, R. A., Swindell, E. C., Jamrich, M., Oh, E. C., Swaroop, A., Fisher, S. K. and Reese, B. E. (2013). Development and plasticity of outer retinal circuitry following genetic removal of horizontal cells. J Neurosci, 33, 17847-17862. Keller-Peck, C. R., Feng, G., Sanes, J. R., Yan, Q., Lichtman, J. W. and Snider, W. D. (2001). Glial cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J Neurosci, 21, 6136-6146. Koulen, P., Fletcher, E. L., Craven, S. E., Bredt, D. S. and Wassle, H. (1998). Immunocytochemical localization of the postsynaptic density protein PSD-95 in the mammalian retina. J Neurosci, 18, 10136-10149. Koyasu, T., Kondo, M., Miyata, K., Ueno, S., Miyata, T., Nishizawa, Y. and Terasaki, H. (2008). Photopic electroretinograms of mGluR6-deficient mice. Curr Eye Res, 33, 91-99. Kramer, E. R., Knott, L., Su, F., Dessaud, E., Krull, C. E., Helmbacher, F. and Klein, R. (2006). Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway selection in the limb. Neuron, 50, 35-47. Kretz, A., Jacob, A. M., Tausch, S., Straten, G. and Isenmann, S. (2006). Regulation of GDNF and its receptor components GFR-alpha1, -alpha2 and Ret during development and in the mature retino-collicular pathway. Brain Res, 1090, 1-14. Li, X., Glubrecht, D. D. and Godbout, R. (2010). AP2 transcription factor induces apoptosis in retinoblastoma cells. Genes Chromosomes Cancer, 49, 819-830. Lin, L. F., Doherty, D. H., Lile, J. D., Bektesh, S. and Collins, F. (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science, 260, 1130-1132. Lu, B. and Je, H. S. (2003). Neurotrophic regulation of the development and function of the neuromuscular synapses. J Neurocytol, 32, 931-941. MacNeil, M. A. and Masland, R. H. (1998). Extreme diversity among amacrine cells: implications for function. Neuron, 20, 971-982. Masland, R. H. (2012). The neuronal organization of the retina. Neuron, 76, 266-280. McBride, J. L. and Kordower, J. H. (2002). Neuroprotection for Parkinson's disease using viral vector-mediated delivery of GDNF. Prog Brain Res, 138, 421-432. Miura, G., Wang, M. H., Ivers, K. M. and Frishman, L. J. (2009). Retinal pathway origins of the pattern ERG of the mouse. Exp Eye Res, 89, 49-62. Mograbi, B., Bocciardi, R., Bourget, I., Busca, R., Rochet, N., Farahi-Far, D., Juhel, T. and Rossi, B. (2001). Glial cell line-derived neurotrophic factor-stimulated phosphatidylinositol 3-kinase and Akt activities exert opposing effects on the ERK pathway: importance for the rescue of neuroectodermic cells. J Biol Chem, 276, 45307-45319. Nag, T. C. and Wadhwa, S. (2001). Differential expression of syntaxin-1 and synaptophysin in the developing and adult human retina. J Biosci, 26, 179-191. Naughton, C. K., Jain, S., Strickland, A. M., Gupta, A. and Milbrandt, J. (2006). Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol Reprod, 74, 314-321. Ohnaka, M., Miki, K., Gong, Y. Y., Stevens, R., Iwase, T., Hackett, S. F. and Campochiaro, P. A. (2012). Long-term expression of glial cell line-derived neurotrophic factor slows, but does not stop retinal degeneration in a model of retinitis pigmentosa. J Neurochem, 122, 1047-1053. Oppenheim, R. W., Houenou, L. J., Parsadanian, A. S., Prevette, D., Snider, W. D. and Shen, L. (2000). Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J Neurosci, 20, 5001-5011. Ostenfeld, T., Tai, Y. T., Martin, P., Deglon, N., Aebischer, P. and Svendsen, C. N. (2002). Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. J Neurosci Res, 69, 955-965. Paratcha, G. and Ledda, F. (2008). GDNF and GFRalpha: a versatile molecular complex for developing neurons. Trends Neurosci, 31, 384-391. Pinto, L. H., Invergo, B., Shimomura, K., Takahashi, J. S. and Troy, J. B. (2007). Interpretation of the mouse electroretinogram. Doc Ophthalmol, 115, 127-136. Prasad, S. and Galetta, S. L. (2011). Anatomy and physiology of the afferent visual system. Handb Clin Neurol, 102, 3-19. Rowan, S. and Cepko, C. L. (2004). Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter. Dev Biol, 271, 388-402. Sakai, T., Wakizaka, A., Matsuda, H., Nirasawa, Y. and Itoh, Y. (1998). Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in Ondine-Hirschsprung syndrome. Pediatrics, 101, 924-926. Salvatore, D., Barone, M. V., Salvatore, G., Melillo, R. M., Chiappetta, G., Mineo, A., Fenzi, G., Vecchio, G., Fusco, A. and Santoro, M. (2000). Tyrosines 1015 and 1062 are in vivo autophosphorylation sites in ret and ret-derived oncoproteins. J Clin Endocrinol Metab, 85, 3898-3907. Samuel, M. A., Zhang, Y., Meister, M. and Sanes, J. R. (2011). Age-related alterations in neurons of the mouse retina. J Neurosci, 31, 16033-16044. Shirato, S., Maeda, H., Miura, G. and Frishman, L. J. (2008). Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves. Exp Eye Res, 86, 914-928. Sonntag, S., Dedek, K., Dorgau, B., Schultz, K., Schmidt, K. F., Cimiotti, K., Weiler, R., Lowel, S., Willecke, K. and Janssen-Bienhold, U. (2012). Ablation of retinal horizontal cells from adult mice leads to rod degeneration and remodeling in the outer retina. J Neurosci, 32, 10713-10724. Tanabe, K., Takahashi, Y., Sato, Y., Kawakami, K., Takeichi, M. and Nakagawa, S. (2006). Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells. Development, 133, 4085-4096. Taylor, L., Arner, K., Engelsberg, K. and Ghosh, F. (2013). Effects of glial cell line-derived neurotrophic factor on the cultured adult full-thickness porcine retina. Curr Eye Res, 38, 503-515. Thoreson, W. B. and Mangel, S. C. (2012). Lateral interactions in the outer retina. Prog Retin Eye Res, 31, 407-441. Ueno, S., Nishiguchi, K. M., Tanioka, H., Enomoto, A., Yamanouchi, T., Kondo, M., Yasuma, T. R., Yasuda, S., Kuno, N., Takahashi, M. and Terasaki, H. (2013). Degeneration of Retinal ON Bipolar Cells Induced by Serum Including Autoantibody against TRPM1 in Mouse Model of Paraneoplastic Retinopathy. PLoS One, 8, e81507. Uesaka, T., Jain, S., Yonemura, S., Uchiyama, Y., Milbrandt, J. and Enomoto, H. (2007). Conditional ablation of GFRalpha1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype. Development, 134, 2171-2181. Voigt, T. (1986). Cholinergic amacrine cells in the rat retina. J Comp Neurol, 248, 19-35. Wang, C. Y., Yang, F., He, X. P., Je, H. S., Zhou, J. Z., Eckermann, K., Kawamura, D., Feng, L., Shen, L. and Lu, B. (2002). Regulation of neuromuscular synapse development by glial cell line-derived neurotrophic factor and neurturin. J Biol Chem, 277, 10614-10625. Wang, X. (2013). Structural studies of GDNF family ligands with their receptors-Insights into ligand recognition and activation of receptor tyrosine kinase RET. Biochim Biophys Acta, 1834, 2205-2212. Wells, S. A., Jr. and Santoro, M. (2009). Targeting the RET pathway in thyroid cancer. Clin Cancer Res, 15, 7119-7123. Yang, F., Feng, L., Zheng, F., Johnson, S. W., Du, J., Shen, L., Wu, C. P. and Lu, B. (2001). GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons. Nat Neurosci, 4, 1071-1078. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58641 | - |
dc.description.abstract | 視網膜屬於一種神經網路,具有特化的細胞把光能轉為神經訊號,最終傳回大腦形成視覺訊息。GDNF family of ligands (GFL)為一群神經滋養因子,根據先前文獻指出GFL和神經元的發育、分化和維持有關。在GFL啟動下游的訊息傳遞前,需要透過活化Rearranged during transfection (Ret)共同接受體方能進行。過去的研究發現到Ret一旦產生基因缺失,在神經系統中會造成視網膜不正常的生理變化,同時造成視網膜的水平細胞和雙極細胞形態產生變異。然而,具有Ret基因缺失的基因轉殖鼠出生後由於腎臟的發育缺損,存活不超過21天,因此無法更進一步探討Ret對於視網膜的影響。本研究目的藉由條件敲毀Ret在視網膜的表現,進而審視正常Ret在視網膜發育完全後,甚至是面對老化時,所扮演可能的角色。
本研究第一個部分先透過免疫組織化學染色了解正常老鼠視網膜的Ret表現。第二個部分是利用Chx10-Cre;C-Retlx/lx基因轉殖鼠(在視網膜條件敲毀Ret基因)探討Ret在視網膜功能。利用蘇木精染色、免疫組織化學染色和西方點墨法,檢驗出生後2個月、4個月、12個月和24個月的小鼠視網膜變化。研究結果顯示正常Ret會表現在視網膜的水平細胞的神經突出(process)和神經節的神經纖維上。在Ret缺失下,視網膜的組織結構產生變異,在出生後12和24個月時outer plexiform layer (OPL)變得較薄,且排列紊亂。深入分析組成該層的水平細胞和感光細胞出現不同形態變化:水平細胞的神經突出在出生後2個月、4個月大幅減少,在出生後12個月、24個月更是明顯。感光細胞則是在出生後12個月、24個月時出現神經突出部分縮回到outer nuclear layer (ONL),而其突觸(synapse) 在ONL產生異位性突觸。西方點墨法分析GFL/Ret下游訊息傳遞,發現到視網膜內的pAkt和pErk的蛋白質表現並沒有因為Ret基因缺失而有明顯改變。 本研究結果推斷Ret對於視網膜的水平細胞的突出甚為重要,由正常的訊息傳遞能維持其基本形態,進而鞏固OPL的組織結構,並讓感光細胞因此不易產生退化。 | zh_TW |
dc.description.abstract | Retina, one of neural networks, contains various specialized cells transducing photons into electric impulses to process visual information in the brain. GDNF family of ligands (GFL), a group of neurotrophic factors, is involved in development, differentiation and maintenance of neurons. GFLs could not activate the downstream signaling pathways until the receptor, rearranged during transfection (Ret), recruited. It is reported that aberrant retinal activity and abnormal morphology of horizontal cells and bipolar cells were detected in Ret mutant mice. However, Ret mutant mice died by day 21 after birth because of kidney agenesis. The aim of this study is to examine the consequences of Ret dysfunction in mature and aged retina.
In our study, we identified the specific cells expressing Ret in the wild-type retina by IHC staining. Next, we examined the consequences in Chx10-Cre;C-Retlx/lx retinae with conditional knockout of Ret. The 2, 4, 12 and 24-month-old transgenic mice were analyzed by hematoxylin staining, IHC staining and western blot. The results showed Ret was expressed in the processes of horizontal cells and nerve fibers of ganglion cells of retina in the wild-type mice. In Chx10-Cre;C-Retlx/lx mice, it displayed the thinner and disorganized OPL at age of 12 months and 24 months. To examine the component in this layer, we found the number of processes of horizontal cells decreased at age of 2 and 4 months, even progressively at age of 12 and 24 months. Additionally, the synapses of photoreceptors were decreased and mislocalized at age of 12 months and 24 months Chx10-Cre;C-Retlx/lx mice. From our western blot analysis, it showed no obvious changes in pAkt and pErk by Ret dysfunction. These results suggest that Ret is important to maintain the processes of horizontal cells and then preserve the integrity of the OPL; consequently, photoreceptors are not easily induced by the transneuronal degeneration. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:23:32Z (GMT). No. of bitstreams: 1 ntu-103-R00446007-1.pdf: 7343737 bytes, checksum: 93ebad3c13504abc9e49bfb3c695cb25 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書…………………………………………………………i
誌謝………………………………………………………..……………….ii 中文摘要…..……………………………………………………...……….iii Abstract …………………………………………….……………..……….v Chapter 1 Introduction…………………………………….....……………..1 Chapter 2 Materials and methods………………………...……………..…..6 Chapter 3 Results ………………………......…………………….……….10 Chapter 4 Discussion ……………………….........………………….…….15 Reference………………………………………………………….………20 Figure legends…………….................................................................25 Supplemental data………………………………………………………...51 | |
dc.language.iso | en | |
dc.title | Ret在視網膜退化扮演角色之探討 | zh_TW |
dc.title | The Role of Ret in Retinal Degeneration | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 盧國賢(Kuo-Shyan Lu),王南凱(Nan-Kai Wang.) | |
dc.subject.keyword | GDNF family of ligands,Ret,視網膜退化,水平細胞,感光細胞, | zh_TW |
dc.subject.keyword | GDNF family of ligands,Ret,retinal degeneration,horizontal cell,photoreceptor, | en |
dc.relation.page | 68 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-01-24 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 7.17 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。