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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46978Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 林中天 | |
| dc.contributor.author | Li-Ya Weng | en |
| dc.contributor.author | 翁麗雅 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:44:30Z | - |
| dc.date.available | 2010-08-20 | |
| dc.date.copyright | 2010-08-20 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-19 | |
| dc.identifier.citation | References
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(1998). Animal models of human retinal dystrophies. Eye (Lond) 12 , 566-70. Petersen-Jones, S. M. (1998). A review of research to elucidate the causes of the generalized progressive retinal atrophies. Vet J 155, 5-18. Petersen-Jones, S. M., D. D. Entz, et al. (1999). cGMP phosphodiesterase-alpha mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog. Invest Ophthalmol Vis Sci 40, 1637-44. Portera-Cailliau, C., C. H. Sung, et al. (1994). Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. Proc Natl Acad Sci U S A 91, 974-8. Rapp, L. M., P. L. Fisher, et al. (1994). Reduced rate of rod outer segment disk synthesis in photoreceptor cells recovering from UVA light damage. Invest Ophthalmol Vis Sci 35, 3540-8. Shahinfar, S., D. P. Edward, et al. (1991). A pathologic study of photoreceptor cell death in retinal photic injury. Curr Eye Res , 47-59. Stone, J., J. Maslim, et al. (1999). Mechanisms of photoreceptor death and survival in mammalian retina. Prog Retin Eye Res 18, 689-735. Swaroop, A., J. Z. Xu, et al. (1992). A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proc Natl Acad Sci U S A 89, 266-70. Vilboux, T., G. Chaudieu, et al. (2008). Progressive retinal atrophy in the Border Collie: a new XLPRA. BMC Vet Res 4, 10. Wang, W., G. M. Acland, et al. (1999). Evaluation of cGMP-phosphodiesterase (PDE) subunits for causal association with rod-cone dysplasia 2 (rcd2), a canine model of abnormal retinal cGMP metabolism. Exp Eye Res 69, 445-53. Wenzel, A., C. Grimm, et al. (2005). Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24, 275-306. Wenzel, A., C. E. Reme, et al. (2001). The Rpe65 Leu450Met variation increases retinal resistance against light-induced degeneration by slowing rhodopsin regeneration. J Neurosci 21, 53-8. Wu, J., S. Seregard, et al. (2006). Photochemical damage of the retina. Surv Ophthalmol 51, 461-81. Yang-Feng, T. L. and A. Swaroop (1992). Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2. Genomics 14, 491-2. Zangerl, B., O. Goldstein, et al. (2006). Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88, 551-63. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46978 | - |
| dc.description.abstract | 摘要
漸進性視網膜萎縮症是一群犬隻傳性視網膜感光細胞基因突變致使漸行性失明的疾病，與人類色素性視網膜炎遺的臨床表現與生理病理學上相似，而Nrl gene突變已經被證實會導致人類色素性視網膜炎。視網膜感光細胞凋零導致其臨床症狀，初期喪失暗視野視力，漸漸失去亮視野的視力，最終造成失明；至今在臨床上仍無有效的治療方式。光誘導的視網膜病變可造成快速且全面性的感光細胞凋亡，在研究上用以模擬遺傳性視網膜病變之動物模式。本實驗使用八週齡Sprague-Dawley大鼠暴露於1500-2000勒克斯的光照下，每日12小時，連續兩天之後，立即將Nrl基因轉殖入視網膜，而後每週以視網膜電波圖評估其視網膜功能變化，並且利用TUNEL染色偵測光照後第一、三、五、七天視網膜細胞凋零的程度，並於每週進行視網膜的免疫螢光染色，以及量測視網膜外核層的厚度作為視網膜結構上變化的評估。結果發現，光照之後在Nrl治療組與對照組皆造成視網膜感光細胞凋零、視網膜電波圖a、b波高度與外核層厚度下降。Nrl基因在轉殖後三天分別在視網膜色素性上皮層、感光細胞外層與外核層偵測到，並且持續表現四週。在視網膜功能保存上，Nrl治療組的視網膜電波圖a 波下降程度較控制組少，並且在基因轉殖後第一至三週兩組間有統計上的顯著差異。在視網膜結構方面， Nrl基因的表現可有效減少轉染區域的視網膜外核層細胞凋亡數目；在基因轉殖後第一週到第三週，Nrl治療可減緩視網膜外核層厚度減少的程度，並與對照組有統計上的顯著差異。Nrl基因的表現可活化成熟的視網膜神經性細胞表現rhodopsin，此外，由免疫組織染色法觀察到轉殖入Nrl基因之細胞可表現桿狀感光細胞、無軸突細胞與水平細胞之細胞標誌。由上述研究結果顯示，轉殖Nrl基因入光誘導視網膜病變大鼠模式之視網膜，可有效地保護視網膜結構與功能的退化。 | zh_TW |
| dc.description.abstract | Abstract
Progressive retinal atrophy (PRA) is a large group of canine inherited retinal diseases. Both PRA and retinitis pigmentosa (RP), the human homologue of PRA, share a similar clinical pathology and phenotype. Photoreceptor apoptosis leads to clinical signs of progressive loss of peripheral and night vision (rod cells) leading to loss of central and day vision (cone cells). There is no clinically effective treatment for inherited retinopathy to date. Light-induced retinopathy provides fast, synchronic photoreceptor apoptosis to mimic the inherited retinal degeneration. The mutation of neural retina leucine zipper (Nrl) gene has been shown to induce RP. 8 week-old Sprague-Dawley rats were maintained in 1500-2000 lux of cyclic light for 2 days. A mixture of Nrl gene and FuGene was introduced into eyes by subretinal injection immediately after light exposure. Retinal function was evaluated by electroretinography (ERG) before light exposure and weekly for 4 weeks (28 days) after gene delivery. Photoreceptor cell death was quantified by TUNEL assay at 1, 3, 5, and 7 days after light exposure and by measuring thickness of the outer nuclear layer (ONL) in the retina before exposure and each week after gene delivery. Retinas were harvested for immunohistochemistry studies every week till 1 month (28 days). Decrements of amplitude of ERG waves and ONL thickness, and the positive TUNEL results showed that the light-induced retinopathy in a rat model was successfully established. The Nrl gene transfection was detected by green fluorescence protein (GFP) and observed in cytoplasm of retinal pigmented epithelium (RPE), outer segment (OS) and ONL during 4 weeks after delivery, then diminished progressively. Significant retinal function preservation was observed at 3 weeks after gene delivery, the preservation of retinal ONL was also observed in the Nrl gene treated group at the first three weeks after gene delivery. TUNEL assay showed similar results of photoreceptor protection against apoptosis as well. In retinal immunohistochemistry, Nrl gene activated the expression of rhodopsin in the mature neuroretinal cells. Some transfected cells expressed positive cell markers of RPE65 for RPE, and syntaxin for amarcrine cells and horizontal cells, respectively. Based on this study, subretinal delivery of Nrl gene may provide functional and morphological preservation against photoreceptor degeneration following light-induced retinal degeneration. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:44:30Z (GMT). No. of bitstreams: 1 ntu-99-R95629040-1.pdf: 3527097 bytes, checksum: 7b5f282ed65022826846863cffa62d50 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | Contents
Acknowledgements i Figure Contents iii Abstract iv Abstract (Chinese version) vi Introduction 1 Aims 9 Materials and Methods 10 Results 16 Discussion 22 Conclusion 27 References 28 Appendix 72 | |
| dc.language.iso | en | |
| dc.subject | 遺傳性視網膜退化症 | zh_TW |
| dc.subject | Nrl基因 | zh_TW |
| dc.subject | 光照誘發視網膜退化模式 | zh_TW |
| dc.subject | Nrl Gene | en |
| dc.subject | inherital retinal degneration | en |
| dc.subject | Light-induced Retinopathy | en |
| dc.title | 視網膜下腔轉殖Nrl基因在大鼠光照誘發視網膜退化模式的作用 | zh_TW |
| dc.title | The Effects of Subretinal Delivery of Nrl Gene on Light-induced Retinopathy in a Rat Model | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 李憶菁 | |
| dc.contributor.oralexamcommittee | 劉振軒,李怡萱,詹東榮 | |
| dc.subject.keyword | Nrl基因,光照誘發視網膜退化模式,遺傳性視網膜退化症, | zh_TW |
| dc.subject.keyword | Nrl Gene,Light-induced Retinopathy,inherital retinal degneration, | en |
| dc.relation.page | 74 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-19 | |
| dc.contributor.author-college | 獸醫專業學院 | zh_TW |
| dc.contributor.author-dept | 臨床動物醫學研究所 | zh_TW |
| Appears in Collections: | 臨床動物醫學研究所 | |
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