跳到主要內容

臺灣博碩士論文加值系統

(44.222.196.236) 您好!臺灣時間:2024/03/29 19:25
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:邱蘭棻
研究生(外文):Lan-Fen Chiou
論文名稱:表沒食子兒茶酚沒食子酸對大鼠視神經軸突截斷後神經節細胞的保護作用
論文名稱(外文):The protective effects of Epigallocatechin-3-gallate (EGCG) on retinal ganglion cells after optic nerve axotomy in rats.
指導教授:陳朝峰陳朝峰引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:76
中文關鍵詞:視神經軸突截斷
外文關鍵詞:optic nerve axotomy
相關次數:
  • 被引用被引用:0
  • 點閱點閱:237
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
表沒食子兒茶酚沒食子酸 (Epigallocatechin-3-gallate, EGCG),屬於綠茶中兒茶素的主要成份之一,具有非常強大之抗氧化能力。
本實驗的目的為觀察EGCG在視神經軸突截斷之動物,是否可保護視網膜神經節細胞,並且更進一步探討其保護效應的機制。
我們使用雌性之Wistar大鼠,先由上丘(superior colliculus)注射5% Fluorogold來標示視網膜神經節細胞。並在眼球後方1 mm處將視神經軸突截斷。在手術進行前30分鐘,先以腹腔注射EGCG (50 mg/kg),在手術後2天及4天時各增一劑,第7天時計數神經節細胞之存活率。結果發現,神經節細胞之存活率由對照組的45.9%顯著提升至EGCG組的58.1% (p=0.017)。
利用西方墨點法偵測蛋白含量得知:GFAP的表現量在手術後第3天即顯著增加,可持續至第7天,但給EGCG後發現在第5天時GFAP之表現量有顯著被抑制之情形。而p-ERK之表現量在手術後第5天即有顯著增加之情況,給予EGCG更增加其表現量。此外,利用眼內注射給予U0126 (200 pmol)抑制MAPK/ERK路徑,發現抑制p-ERK可將EGCG促進細胞存活能力阻斷。顯示MAPK/ERK路徑可能參與EGCG之神經保護作用。同時我們也觀察到促進細胞凋亡分子Bax之表現在在手術後第5天有顯著增加,給予EGCG後表現量則被抑制。而抗細胞凋亡之蛋白Bcl-2則無顯著差異。nNOS在手術後第3天表現量即顯著上升,同樣可持續至第7天。給予EGCG後第5天能使其表現量下降,顯示EGCG之保護性可能和調控NO有關。最後我們也探討另一條與促進細胞存活有關之PI3-K/Akt路徑,發現在手術後第1天p-Akt表現量即顯著增加,可持續至第5天。而給予EGCG發現於第3天時可使其表現量更增加。利用眼內注射給予LY294002 (200 pmol)抑制PI-3K/Akt路徑,發現抑制p-Akt可將EGCG促進細胞存活能力阻斷。顯示PI3-K/Akt路徑亦可能參與EGCG之神經保護作用。
綜合以上,我們認為在此視神經軸突截斷模式中,EGCG之保護效應於第五天可能為關鍵之時間點。而EGCG可能透過活化MAPK/ERK與PI3-K/Akt之訊息傳遞路徑對視網膜神經節細胞展現其神經保護效應。
目次………………………….………………………………………………………I
縮寫表……………………………….………………….………………….………V
中文摘要………………………………………..…….…………………..……..VII
英文摘要……………………………...………………………………...………..IX
圖次……...………....................................................................................................XI
一、文獻回顧
1、視網膜……………………………………………………………….………...1
1-1 視網膜的解剖構造及其生理功能…………………….…………………....1
1-2 視網膜神經節細胞…………………………………………….…………....1
1-3 視網膜的病變…………………………………………………….………....2
1-4 視網膜病變的研究模式………………………………………….………....2
2、視神經軸突截斷(optic nerve axotomy)…………….……………….….2
2-1引言……………………………………………………………….…...……..2
2-2視神經軸突截斷造成視網膜神經節細胞死亡模式…………………..…....3
2-3提升視網膜神經節細胞存活率之神經滋養因子...………………….….….4
3、膠質纖維酸性蛋白(glial fibrillary acidic protein;GFAP)….….….4
4、神經元一氧化氮合成酶(neuronal nitric oxide synthase; nNOS)…..5
5、細胞存活路徑(cell survival pathway)…………………………………...6
6、細胞凋亡(apoptosis)………………………………………………………..8
7、兒茶素(catechin)……………………………...……………….………...…..9
7-1引言……………………………….……………………………………..…..9
7-2兒茶素展現神經保護透過之機制….…………………………………....…9
7-2-1 抗氧化能力:清除ROS且提升內生性抗氧化物…….……………9
7-2-2 細胞內訊息傳遞路徑…………………………………….……..…..10
7-2-2-1 Protein kinase C…...…………………………………………...10
7-2-2-2其他訊息傳遞路徑…...………………………………………..10
7-2-3 抵抗細胞凋亡…….…………………………………………...…….11
7-2-4 金屬螯合能力…………………………………………………….....11
7-3 EGCG於動物模式中展現神經保護效應………………………………....11
7-4 EGCG對視網膜之保護…………………………………………………....12
二、研究目的…………………………………………………………………….13
三、研究材料與方法………………………………………………………...14
1、動物處理...………………………………………..…………...……….…...14
1-1實驗動物的準備………………………………...……………………….…14
1-2逆行標記視網膜神經節細胞…………………………………………....…14
1-3視神經軸突截斷之手術………………………………………………....…15
1-4藥物的給予……………………………………………………………....…15
1-4-1 腹腔注射.……………………….………………………….…………15
1-4-2 玻璃體內注射………………………………………………………...15
1-5 視網膜神經節細胞的計數………………………………………………...16
2、視網膜檢體處理……………………………………...……………………..17
2-1 西方墨點分析(Western blotting analysis):.……………………………….17
2-1-1 西方墨點法的檢體製備…………………………………...................17
2-1-2 西方墨點法分析…………………………………………...................17
2-1-3 呈色反應…………………………………………………...................20
3、資料處理與統計方法………...………………………..…………………...20
四、結果………………………………...………………………………..……….21
1、EGCG對視神經軸突截斷7天後的視網膜神經節細胞存活率之影響.…………………………………………………………………………..21
2、EGCG對視神經軸突截斷後GFAP表現量之影響.………………..21
3、EGCG對視神經軸突截斷後p-ERK1/2表現量之影響...….………21
4、玻璃體內注射U0126 (p-ERK 抑制劑)後,EGCG對視神經軸突截斷7天後之影響. .……………..…...………………………….……….22
4-1對視神經軸突截斷5天後的p-ERK1/2表現量之影響.………………….22
4-2對視神經軸突截斷7天後的視網膜神經節細胞存活率之影響.…………22
5、EGCG對視神經軸突截斷後Bax表現量之影響.………………….22
6、EGCG對視神經軸突截斷後Bcl-2表現量之影響.………………..23
7、EGCG對視神經軸突截斷後nNOS表現量之影響.……………….23
8、EGCG對視神經軸突截斷後p-Akt表現量之影響.…………….….23
9、玻璃體內注射LY294002 (p-Akt 抑制劑)後,EGCG對視神經軸突截斷7天後之影響…….………………………………………………23
9-1對視神經軸突截斷3天後的p-Akt表現量之影響…….………………24
9-2對視神經軸突截斷7天後的視網膜神經節細胞存活率之影響………24
五、討論………………………………………………………...………………..25
1、視網膜受傷害之指標…….………………….…………………….………25
1-1計數視網膜神經細胞方面.…………………….…………………………..26
1-2蛋白表現:GFAP.…………………….……………………………………26
2、EGCG展現神經保護效應與機制……………………….……………...27
2-1 EGCG在其他神經系統受傷害之保護效應.……………………………...27
2-2 EGCG對於視網膜傷害之益處.…………………….……………………..27
2-3透過活化ERK、Akt或其他路徑.…………………….…………………..28
3、單純視神經軸突截斷即可活化ERK?…………………….………..29
3-1 ERK增加之時間點.…………………….………………………………….29
3-2抑制劑專一性.…………………….………………………,….……………29
4、細胞凋亡路徑亦參與EGCG展現之神經保護作用.………………..30
4-1 Bax蛋白之表現量變化.…………………….……………………………...31
4-2 Bcl-2蛋白之表現量變化.…………………….……………………………32
5、EGCG對視神經軸突截斷後nNOS表現量之影響.………..……….33
6、單純視神經軸突截斷即可活化Akt?.……………………….………..33
六、結論………………………………………………………………………….35
七、圖次….…………………………………………….…………………………36
八、參考文獻……………………………………...…………..………………..66
Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 281:
1322-1326, 1998.

Akiyama H., Nakazawa T., Shimura M., Tomita H., Tamai M. Presence of mitogen-activated protein kinase in retinal Müller cells and its neuroprotective effect ischemia-reperfusion injury. Neuroreport. 13(16):2103-2107, 2002.

Alessandrini A., Namura S., Moskowitz MA., Bonventre JV. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc Natl Acad Sci U S A. 96(22):12866-12869, 1999.

Berkelaar M., Clarke DB., Wang YC., Bray GM., Aguayo AJ. Axotomy Results in Delayed Death and Apoptosis of Retinal Ganglion Cells in Adult Rats. J Neurosci. 14(7):4368-4374, 1994.

Blanco AR., Sudano-Roccaro A., Spoto GC., Nostro A., Rusciano D. Epigallocatechin gallate inhibits biofilm formation by ocular staphylococcal isolates. Antimicrob Agents Chemother. 49(10):4339-4343, 2005.

Brandstätter JH., Koulen P., Wässle H. Diversity of glutamate receptors in the mammalian retina. Vision Res. 38(10):1385-1397, 1998.

Bruno V., Scapagnini U., Canonico PL. Excitatory amino acids and neurotoxicity. Funct Neurol. 8(4):279-292, 1993. Review.

Cardell M., Wieloch T. Time course of the translocation and inhibition of protein kinase C during complete cerebral ischemia in the rat. J Neurochem. 1308-1314, 1993.

Carmignoto G., Maffei L., Candeo P., Canella R., Comelli C. Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. J Neurosci. 9(4):1263-1272, 1989.



Chen JH., Tipoe GL., Liong EC., So HS., Leung KM., Tom WM., Fung PC., Nanji AA. Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants. Am J Clin Nutr. 80(3):742-751, 2004.

Chen H., Weber AJ. Expression of Glial Fibrillary Acidic Protein and Glutamine Synthetase by Müller Cells After Optic Nerve Damage and Intravitreal Application of Brain-Derived Neurotrophic Factor. Glia 38:115–125, 2002.

Cheon EW., Park CH., Kang SS., Cho CJ., Yoo JM., Song JK., Choi WS. Change in endothelial nitric oxide synthase in the rat retina following transient ischemia. Neuroreport. 14:329-333, 2003.

Chierzi S, Fawcett JW. Regeneration in the mammalian optic nerve. Restor Neurol Neurosci. 19(1-2):109-118, 2001. Review.

Chierzi S., Strettoi E., Cenni MC., Maffei L. Optic nerve crush: axonal responses in wild-type and bcl-2 transgenic mice. J Neurosci. 19(19):8367-8376, 1999.

Chung JH., Han JH., Hwang EJ., Seo JY., Cho KH., Kim KH., Youn JI., Eun HC. Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes. FASEB J. 17(13):1913-1915, 2003.

Clarke DB., Bray GM., Aguayo AJ. Prolonged administration of NT-4/5 fails to rescue most axotomized retinal ganglion cells in adult rats. Vision Res. 38(10):1517-1524, 1998.

Cui Q., Yip HK., Zhao RC., So KF., Harvey AR. Intraocular elevation of cyclic AMP potentiates ciliary neurotrophic factor-induced regeneration of adult rat retinal ganglion cell axons. Mol Cell Neurosci. 22(1):49-61, 2003.

Dawson TM., Dawson VL., Snyder SH. Molecular mechanisms of nitric oxide actions in the brain. Ann N Y Acad Sci. 738:76-85, 1994.

Deckwerth TL., Johnson EM Jr. Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor. J Cell Biol. 123:1207-1222, 1993.

DiLoreto DA Jr., Martzen MR., del Cerro C., Coleman PD., del Cerro M. Müller cell changes precede photoreceptor cell degeneration in the age-related retinal degeneration of the Fischer 344 rat. Brain Res. 698(1-2):1-14, 1995.

Dreyer EB., Pan ZH., Storm S., Lipton SA. Greater sensitivity of larger retinal ganglion cells to NMDA-mediated cell death. Neuroreport. 5(5):629-631, 1994.

Eitan S., Solomon A., Lavie V., Yoles E., Hirschberg DL., Belkin M., Schwartz M. Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264(5166):1764-1768, 1994.

Fischer D., He Z., Benowitz LI. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci. 24(7):1646-1651, 2004.

Garcia I., Martinou I., Tsujimoto Y., Martinou JC. Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science 258:302-304, 1992.

Garcia-Valenzuela E., Shareef S., Harris A., Chung HS. Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res. 61:33-44, 1995.

Gingery A., Bradley EW., Pederson L., Ruan M., Horwood NJ., Oursler MJ. TGF-beta coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival. Exp Cell Res. 2008.

Goldstein IM, Ostwald P, Roth S. Nitric oxide: a review of its role in retinal function and Disease. Vision Res 36:2979-2994, 1996.

Grinberg LN., Newmark H., Kitrossky N., Rahamim E., Chevion M., Rachmilewitz EA. Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol. 54(9):973-978, 1997.

Groppe M., Thanos S., Schuhmann W., Heiduschka P. Measurement of nitric oxide production by the lesioned rat retina with a sensitive nitric oxide electrode. Anal Bioanal Chem. 376(6):797-807, 2003.


Han BH., Holtzman DM. BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J Neurosci. 20(15):5775-5781, 2000.

Hayashi Y., Kitaoka Y., Munemasa Y., Ohtani-Kaneko R., Kikusui T., Uematsu A., Takeda H., Hirata K., Mori Y., Ueno S. Neuroprotective Effect of 17β-Estradiol Against N-Methyl-D-Aspartate-Induced Retinal Neurotoxicity Via p-ERK Induction. J Neurosci Res. 85:386–394, 2007.

Henderson RG., Fernald RD. Timing and location of rhodopsin expression in newly born rod photoreceptors in the adult teleost retina. Brain Res Dev Brain Res. 151(1-2):193-197, 2004.

Heiduschka P., Thanos S. Cortisol promotes survival and regeneration of axotomised retinal ganglion cells and enhances effects of aurintricarboxylic acid. Graefes Arch Clin Exp Ophthalmol. 244(11):1512-1521, 2006.

Hockenbery D., Nunez G., Milliman C., Schreiber RD., Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334-336, 1990.

Huxlin KR., Dreher Z., Schulz M., Dreher B. Glial reactivity in the retina of adult rats. Glia. 15(2):105-118, 1995.

Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci. 20(3):132-139, 1997. Review.

Isenmann S., Wahl C., Krajewski S., Reed JC., Bähr M. Up-regulation of Bax Protein in Degenerating Retinal Ganglion Cells Precedes Apoptotic Cell Death after Optic Nerve Lesion in the Rat. Eur J Neurosci. 9:1763-1772, 1997.

Kang WS., Lim IH., Yuk DY., Chung KH., Park JB., Yoo HS., Yun YP. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb Res. 96(3):229-237, 1999.

Kermer P., Ankerhold R., Klöcker N., Krajewski S., Reed JC., Bähr M. Caspase-9: involvement in secondary death of axotomized rat retinal ganglion cells in vivo. Brain Res Mol Brain Res. 85(1-2):144-150, 2000.

Kermer P., Klöcker N., Labes M., Bähr M. Insulin-Like Growth Factor-I Protects Axotomized Rat Retinal Ganglion Cells from Secondary Death via PI3-K-Dependent Akt Phosphorylation and Inhibition of Caspase-3 In Vivo. J Neurosci. 20(2):2-8, 2000.

Kilic U., Kilic E., Soliz J., Bassetti CI., Gassmann M., Hermann DM. Erythropoietin protects from axotomy-induced degeneration of retinal ganglion cells by activating ERK-1/-2. FASEB J.19(2):249-251, 2004.

Kilic U., Kilic E., Järve A., Guo Z., Spudich A., Bieber K., Barzena U., Bassetti CL., Marti HH., Hermann DM. Human Vascular Endothelial Growth Factor Protects Axotomized Retinal Ganglion Cells In Vivo by Activating ERK-1/2 and Akt Pathways. J Neurosci. 26(48):12439 –12446, 2006.

Kim IB., Kim KY., Joo CK., Lee MY., Oh SJ., Chung JW., Chun MH. Reaction of Müller cells after increased intraocular pressure in the rat retina. Exp Brain Res. 121(4):419-424, 1998.

Klöcker N., Bräunling F., Isenmann S., Bähr M. In vivo neurotrophic effects of GDNF on axotomized retinal ganglion cells. Neuroreport. 8(16):3439-3442, 1997.

Klöcker N., Kermer P., Gleichmann M., Weller M., Bähr M. Both the neuronal and inducible isoforms contribute to upregulation of retinal nitric oxide synthase activity by brain-derived neurotrophic factor. J Neurosci. 19(19):8517-8527, 1999.

Koeberle PD., Ball AK. Nitric oxide synthase inhibition delays axonal degeneration and promotes the survival of axotomized retinal ganglion cells. Exp Neurol. 158(2):366-381, 1999.

Koh SH., Lee SM., Kim HY., Lee KY., Lee YJ., Kim HT., Kim J., Kim MH., Hwang MS., Song C., Yang KW., Lee KW., Kim SH., Kim OH. The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett. 395(2):103-107, 2006.

Ko ML., Hu DN., Ritch R., Sharma SC., Chen CF. Patterns of retinal ganglion cell survival after brain-derived neuritrophic factor administration in hypertensive eyes of rats. Neurosci Lett. 305:139-142, 2001.

Kolb H., Linberg KA., Fisher SK. Neurons of the human retina: a Golgi study. J Comp Neurol. 318(2):147-187, 1992.

Kretz A., Schmeer C., Tausch S., Isenmann S. Simvastatin promotes heat shock protein 27 expression and Akt activation in the rat retina and protects axotomized retinal ganglion cells in vivo. Neurobio Dis. 21:421- 430, 2006.

Lam TK., Chan WY., Kuang GB., Wei H., Shum AS., Yew DT. Differential expression of glial fibrillary acidic protein (GFAP) in the retinae and visual cortices of rats with experimental renal hypertension. Neurosci Lett. 198(3):165-168, 1995.

Lee EJ., Kim KY., Gu TH., Moon JI., Kim IB., Lee MY., Oh SJ., Chun MH. Neuronal nitric oxide synthase is expressed in the axotomized ganglion cells of the rat retina. Brain Res. 986:174–180, 2003.

Lee KY., Koh SH., Noh MY., Kim SH., Lee YJ. Phosphatidylinositol-3-kinase activation blocks amyloid beta-induced neurotoxicity. Toxicology. 243(1-2):43-50. 2008.

Levites Y., Amit T., Mandel S., Youdim MB. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J. 17(8):952-954, 2003.

Levites Y., Amit T., Youdim MB., Mandel S. Involvement of protein kinase C activation and cell survival/ cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem. 277(34):30574-30580, 2002.

Levites Y., Youdim MB., Maor G., Mandel S. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem Pharmacol. 63(1):21-29, 2002.

Lieth E., Barber AJ., Xu B., Dice C., Ratz MJ., Tanase D., Strother JM. Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes. 47(5):815-820, 1998.


Lin YL., Lin JK. (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB. Mol Pharmacol. 52(3):465-472, 1997.

Lopez-Costa JJ., Goldstein J., Saavedra JP. Neuronal and macrophagic nitric oxide synthase isoforms distribution in normal rat retina. Neurosci Lett. 232:155-158, 1997.

Lorenz M., Wessler S., Follmann E., Michaelis W., Düsterhöft T., Baumann G., Stangl K., Stangl V. A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem. 279(7):6190-6195, 2004.

Maher P. How protein kinase C activation protects nerve cells from oxidative stress-induced cell death. J Neurosci. 21(9):2929-2938, 2001.

Mandel SA., Avramovich-Tirosh Y., Reznichenko L., Zheng H., Weinreb O., Amit T., Youdim MB. Multifunctional Activities of Green Tea Catechins in Neuroprotection. Neurosignals 14:46–60, 2005. Review.

Mandel S., Maor G., Youdim MB. Iron and alpha-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol (-)-epigallocatechin-3-gallate. J Mol Neurosci. 24(3):401-416, 2004.

Mandel S., Weinreb O., Amit T., Youdim MB. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem. 88:1555–1569, 2004.

Mandel S., Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med. 37(3):304-317, 2004. Review.

Mansour-Robaey S., Clarke DB., Wang YC., Bray GM., Aguayo AJ. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A. 91(5):1632-1636, 1994.


Matsuzaki H., Tamatani M., Yamaguchi A., Namikawa K., Kiyama H., Vitek MP., Mitsuda N., Tohyama M. Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: signal transduction cascades. FASEB J. 15(7):1218-1220, 2001.

Merrill JE. Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Dev Neurosci. 14(1):1-10, 1992. Review.

Nakazawa T., Tamai M., Mori N. Brain-Derived Neurotrophic Factor Prevents Axotomized Retinal Ganglion Cell Death through MAPK and PI3K Signaling Pathways. Invest Ophthalmol Vis Sci. 43:3319–3326, 2002.

Nakazawa T., Shimura M., Tomita H., Akiyama H., Yoshioka Y., Kudou H., Tamai M. Intrinsic activation of PI3K/Akt signaling pathway and its neuroprotective effect against retinal injury. Curr Eye Res. 26(1): 55-63, 2003.

Nakazawa T., Takahashi H., Shimura M. Estrogen has a neuroprotective effect on axotomized RGCs through ERK signal transduction pathway. Brain Res. 1093:141 –149, 2006.

Newman E., Reichenbach A. The Müller cell: a functional element of the retina.
Trends Neurosci. 19(8):307-312, 1996. Review.

Oltvai Z., Milliman C., Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609-619, 1993.

Osborne NN., Casson RJ., Wood JP., Chidlow G., Graham M., Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res. 23(1):91-147, 2004. Review.

Peng PH., Ko ML., Chen CF. Epigallocatechin-3-gallate reduces retinal ischemia/reperfusion injury by attenuating neuronal nitric oxide synthase expression and activity. Exp Eye Res. 86:637-646, 2008.

Rabacchi SA., Bonfanti L., Liu XH., Maffei L. Apoptotic cell death induced by optic nerve lesion in the neonatal rat. J Neurosci.14(9):5292-5301, 1994.

Reznichenko L., Amit T., Youdim MB., Mandel S. Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. J Neurochem. 93(5):1157-1167, 2005.

Rezai-Zadeh K., Shytle D., Sun N., Mori T., Hou H., Jeanniton D., Ehrhart J., Townsend K., Zeng J., Morgan D., Hardy J., Town T., Tan J. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. 25(38):8807-8814, 2005.

Richards A., Emondi AA., Rohrer B. Long-term ERG analysis in the partially light-damaged mouse retina reveals regressive and compensatory changes. Vis Neurosci. 23(1):91-97, 2006.

Schroeter H., Boyd C., Spencer JP., Williams RJ., Cadenas E., Rice-Evans C. MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging. 23(5):861-880, 2002. Review.

Schroeter H., Spencer JP., Rice-Evans C., Williams RJ. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J. 358(Pt 3):547-557, 2001.

Schwartz M. Optic nerve crush: protection and regeneration. Brain Res Bull. 62(6):467-471, 2004. Review.

Schwartz M., Yoles E., Levin LA. ''Axogenic'' and ''somagenic'' neurodegenerative diseases: definitions and therapeutic implications. Mol Med Today. 5(11):470-473, 1999. Review.

Sievers J., Hausmann B., Unsicker K., Berry M. Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve.
Neurosci Lett. 76(2):157-162, 1987.

Snider WD., Elliott JL., Yan Q. Axotomy-induced neuronal death during development. J Neurobiol. 23(9):1231-1246, 1992.



Small DL., Monette R., Chakravarthy B., Durkin J., Barbe G., Mealing G., Morley P., Buchan AM. Mechanisms of 1S,3R-ACPD-induced neuroprotection in rat hippocampal slices subjected to oxygen and glucose deprivation. Neuropharmacology. 35(8):1037-1048, 1996.

Song JM., Lee KH., Seong BL. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 68(2):66-74, 2005.

Takahashi K., Lam TT., Edward DP., Buchi ER., Tso MO. Protective effects of flunarizine on ischemic injury in the rat retina. Arch Ophthalmol. 10(6):862-870, 1992.

Tanihara H., Hangai M., Sawaguchi S., Abe H., Kageyama M., Nakazawa F., Shirasawa E., Honda Y. Up-regulation of glial fibrillary acidic protein in the retina of primate eyes with experimental glaucoma. Arch Ophthalmol. 115(6):752-756, 1997.

Torroglosa S., Villegas-Perez MP. Death and neuroprotection of retinal ganglion cells after different types of injury. Neurotox Res. 2(2-3):215-227, 2000.

Villegas-Pérez MP., Vidal-Sanz M., Bray GM., Aguayo AJ. Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. J Neurosci. 8(1):265-280, 1988.

Villegas-Pérez MP., Vidal-Sanz M., Rasminsky M., Bray GM., Aguayo AJ. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J Neurobiol. 24(1):23-36, 1993.

Ueda Y., Hirai S., Osada S., Suzuki A., Mizuno K., Ohno S. Protein kinase C activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. J Biol Chem. 271(38):23512-23519, 1996.

Watanabe M., Rutishauser U., Silver J. Formation of the retinal ganglion cell and optic fiber layers. J Neurobiol. 22(1):85-96, 1991.

Wick A., Wick W., Waltenberger J., Weller M., Dichgans J., Schulz JB. Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci. 22(15):6401-6407, 2002.
Xu Z., Chen S., Li X., Luo G., Li L., Le W. Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res. 31(10):1263-1269, 2006.

Yoles E., Wheeler LA., Schwartz M. Alpha2-adrenoreceptor agonists are neuroprotective in a rat model of optic nerve degeneration. Invest Ophthalmol Vis Sci. 40(1):65-73, 1999.

Yoshino K., Ogawa K., Miyase T., Sano M. Inhibitory Effects of the C-2 Epimeric Isomers of Tea Catechins on Mouse Type IV Allergy. J Agric Food Chem. 52(15):4660-4663, 2004.

Young JE., Gross KW., Khani SC. Conserved structure and spatiotemporal function of the compact rhodopsin kinase (GRK1) enhancer/promoter. Mol Vis. 11:1041-1051, 2005.

Yun HY., Gonzalez-Zulueta M., Dawson VL., Dawson TM. Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras. Proc Natl Acad Sci U S A. 95(10):5773-5778, 1998.

Zanassi P., Paolillo M., Feliciello A., Avvedimento EV., Gallo V., Schinelli S. cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons. J Biol Chem. 276(15):11487-11495, 2001.

Zecca L., Youdim MB., Riederer P., Connor JR., Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 5(11):863-873, 2004. Review.

Zeevalk GD., Nicklas WJ. Action of the anti-ischemic agent ifenprodil on N-methyl-D-aspartate and kainate-mediated excitotoxicity. Brain Res. 522(1):135-139, 1990.

Zhang B., Osborne NN. Oxidative-induced retinal degeneration is attenuated by epigallocatechin gallate. Brain Res. 1124:176 –187, 2006.

Zhang B., Safa R., Rusciano D., Osborne NN. Epigallocatechin gallate, an active ingredient from green tea, attenuates damaging influences to the retina caused by ischemia/reperfusion. Brain Res. 1159:40 –53, 2007.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top