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硝子体内投与薬物の眼組織障害の研究と臨床応用
http://hdl.handle.net/10232/19905
http://hdl.handle.net/10232/199057118e034-68ef-4516-a2f3-9d7ca1ed1d8a
名前 / ファイル | ライセンス | アクション |
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23791995.pdf (219.4 kB)
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Item type | 研究報告書 / Research Paper(1) | |||||
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公開日 | 2013-10-01 | |||||
タイトル | ||||||
タイトル | 硝子体内投与薬物の眼組織障害の研究と臨床応用 | |||||
タイトルよみ | ||||||
タイトルよみ | ショウシタイナイ トウヨ ヤクブツ ノ ガンソシキ ショウガイ ノ ケンキュウ ト リンショウ オウヨウ | |||||
別言語のタイトル | ||||||
その他のタイトル | Eye tissue damage and clinical application of intra vitreous injection | |||||
著者 |
山下, 高明
× 山下, 高明 |
|||||
著者よみ | ||||||
姓名 | ヤマシタ, タケヒロ | |||||
別言語の著者 | ||||||
姓名 | YAMASHITA, Takehiro | |||||
言語 | ||||||
言語 | jpn | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 眼薬理学 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 硝子体注射 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 網膜色素上皮 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | TNF-α | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 薬物反応性 | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 2011-2012年度科学研究費助成事業(科学研究費補助金(若手研究(B))研究成果報告書 課題番号:23791995 研究代表者:山下高明(鹿児島大学・医学部・歯学部附属病院・助教) | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 硝子体内薬物投与に起因する炎症が網膜色素上皮に与える影響を調べる為に、炎症性サイトカインの代表であるTNF-αについて調査・報告した。当教室で培養可能な極性をもった網膜色素上皮細胞のシートにTNF-αを暴露させると、細胞同士のタイトジャンクション(ZO-1)の破壊が認められた。さらに、TNF-αによるさまざまな細胞内シグナル伝達の中で、MAPキナーゼパスウェイが活性化されることにより、タイトジャンクションの破壊、すなわち外側血液網膜関門の破壊が引き起こされることが分かった。 | |||||
要約(Abstract) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Retinal pigment epithelial (RPE) cells form a blood-ocular barrier, and their polarized property is crucial for maintaining the barrier functions. Tumor necrosis factor alpha (TNF-α), a major pleotropic inflammatory cytokine that disrupts the barrier function and eventual angiogenesis, is expressed in the choroidal neovascularizations of age-related macular degeneration eyes. Thus, it most likely plays an important role in the progression of the disease. The purpose of this study was to compare the effects of TNF-α on the barrier function of polarized RPE cells. Non-polarized RPE cells were used as negative controls. Isolated porcine RPE cells were seeded on Transwell™ membranes. The polarization of the RPE cells was determined by their high transepithelial electrical resistance and by their differential secretion of vascular endothelial growth factor (lower layer/upper layer >2.5X). Polarized RPE cells were incubated with 10 ng/ml of TNF-α and the TER was measured. TNF-α significantly decreased the TER of polarized RPE cells by 17.6 ± 2.7% (P < 0.001) of the control at 24 h and that of non-polarized RPE cells by 5.4 ± 6.5% (P = 0.401). The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked the effects of TNF-α of decreasing the TER. Cell junction-related molecules, e.g., ZO-1, located between cells in control RPE cells, were disassembled by TNF-α, and this breakdown was suppressed by SB203580 in polarized RPEs. These results indicate that the breakdown of the RPE barrier function was caused exclusively by TNF-α in polarized RPEs, and TNF-α was acting through the p38 MAPK pathways. Investigations of polarized RPE cells should be more suitable for in vitro studies of the pathophysiology of retinochoroidal diseases. | |||||
作成日 | ||||||
日付 | 2013-04-25 | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
NDC | ||||||
主題Scheme | NDC | |||||
主題 | 496 | |||||
公開者・出版者 | ||||||
出版者 | 鹿児島大学 | |||||
公開者よみ | ||||||
公開者よみ | カゴシマ ダイガク | |||||
公開者別名 | ||||||
公開者別名 | Kagoshima University | |||||
科研費番号 | ||||||
23791995 |