JP6664115B2 - アフリベルセプトによる網膜保護作用 - Google Patents
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- macular degeneration
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Description
以下に示す発明は、主として、本発明者らの検討による上記成果に基づくものである。
[1]アフリベルセプトを有効成分とする、萎縮型加齢黄斑変性症の予防又は治療薬。
[2]アフリベルセプトを有効成分とし、滲出型加齢黄斑変性症の患者に投与されることを特徴とする、萎縮型加齢黄斑変性症の予防薬。
[3]治療上有効量のアフリベルセプトを萎縮型加齢黄斑変性症の患者に投与するステップを含む、萎縮型加齢黄斑変性症の治療方法。
萎縮型加齢黄斑変性症モデルである光誘発網膜障害系においてアフリベルセプトの保護作用を機能的、組織学的に評価した。
マウスを光照射前24時間の暗順応の後、散瞳薬を点眼し、8,000 luxの可視光照射を3時間行う。その後、再び24時間の暗順応を行い、3日間通常光条件下で飼育を行う。光照射から5日後に、ケタミン・キシラジン麻酔下にて網膜電図(ERG)により機能的評価を行う。その直後、頸椎脱臼し安楽死させた後、眼球を摘出し、パラフィン切片の作製を行い、ヘマトキシリン−エオジン染色を用いて組織学的評価を行う。薬物投与は硝子体内投与により行い、イソフルラン麻酔下において、溶媒、アフリベルセプト、又は抗VEGF抗体の投与を光照射の2時間前に行う。
ケタミン・キシラジン混合麻酔を投与した後、ミドリンPにより散瞳させ、マウスの体温を37℃に保ちながら、口腔と臀部にそれぞれ電極を設置し、角膜に記録電極を接触させて測定する。
網膜障害の評価はヘマトキシリン−エオジン染色した標本を用いる。各サンプルにつき3切片を任意に選択し、視神経乳頭中心から240μm間隔で網膜外顆粒層(outer nuclear layer : ONL)の厚みをImage Jを使用して測定する。
網膜電図の評価において、光の暴露により網膜が障害され、a波(視細胞の機能を表す)、b波(ミュラー細胞、双極細胞の機能を表す)ともに波形が減弱したが、アフリベルセプトの投与は波形の減弱を改善した(図1)。また、組織学的評価において、光の暴露により視細胞の存在している外顆粒層(Outer Nuclear Layer: ONL)の菲薄化が認められたが、アフリベルセプトの投与は障害を改善した(図2)。抗VEGF抗体は、光の暴露による網膜機能の低下とONLの菲薄化に影響を与えなかった(図3)。
Claims (2)
- アフリベルセプトを有効成分とする、萎縮型加齢黄斑変性症の予防又は治療薬。
- アフリベルセプトを有効成分とし、滲出型加齢黄斑変性症の患者に投与されることを特徴とする、萎縮型加齢黄斑変性症の予防薬。
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US8821870B2 (en) * | 2008-07-18 | 2014-09-02 | Allergan, Inc. | Method for treating atrophic age related macular degeneration |
EP2714734A1 (en) * | 2011-05-27 | 2014-04-09 | Novartis AG | Method of treating vision disorders |
CA2911041C (en) * | 2012-05-01 | 2020-12-15 | Shelley Romayne BOYD | Methods for treating and diagnosing blinding eye diseases |
WO2015029948A1 (ja) * | 2013-08-26 | 2015-03-05 | リンク・ジェノミクス株式会社 | 網膜色素上皮の障害を原因とする網膜疾患の予防または治療剤 |
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