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網膜における神経-血管-グリア連関の破綻と再構築に関する研究

浅野 大樹 北里大学

2021.07.20

概要

網膜の恒常性は、神経細胞、血管構成細胞 (内皮細胞/平滑筋/周皮細胞) 及びグリア細胞 (アストロサイト/ミクログリア/ミュラー細胞 ) が情報交換することにより維持されている (神経-血管-グリア連関) (Fig. 1)。[1,2]例えば、網膜血管の拡張と収縮及び血液網膜関門の維持には、血管構成細胞のみならず神経細胞及びグリア細胞が関与している。[3,4]また、糖尿病網膜症や緑内障等の網膜疾患では、神経-血管-グリア連関の破綻と病態との関連が示唆されているが、その詳細は不明である。

我々はこれまでに N-methyl-D-aspartic acid (NMDA) を硝子体内に投与したラットの網膜において、1) 視神経節細胞の脱落に遅れてグリア細胞が活性化し、血管が脱落すること、[5-7]2) 神経と血管の相互依存度は幼若期 (2 週齢) において強く、個体の成熟に伴い減弱することを明らかにしている (Fig. 2)。[8]

本研究では、傷害性刺激に対してより脆弱である 1 週齢の新生仔ラットにおいて、視神経節細胞を脱落させて、その後 に生じる網膜血管の変化と血管変化における神経及びグリアの意義について検討することにより、網膜における 神経-血管-グリア連関の破綻と再構築の詳細を明らかにし、網膜疾患の新規予防・治療戦略の礎を構築することを目的とした。

第 1 章では、新生仔ラットの硝子体内に NMDA を投与することにより視神経節細胞を脱落させた後に、網膜血管が脱落し、再形成される過程について検討した。そして、第 2 章及び第 3 章では網膜血管の脱落及び血管形成の機序について、それぞれ検討した。

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