2021 Fiscal Year Final Research Report

Therapeutic strategy for free ATP in retinal macular edema

Research Project

PDF

Project/Area Number	17K11455
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Ophthalmology
Research Institution	Fukuoka University (2019-2021) Kyushu University (2017-2018)
Principal Investigator	Hisatomi Toshio 福岡大学, 医学部, 准教授 (50404033)
Co-Investigator(Kenkyū-buntansha)	園田康平九州大学, 医学研究院, 教授 (10294943) 池田康博九州大学, 医学研究院, 准教授 (20380389) 吉田茂生久留米大学, 医学部, 教授 (50363370)
Project Period (FY)	2017-04-01 – 2022-03-31
Keywords	黄斑浮腫 / 糖尿病 / 透過性亢進 / ATP / VEGF / 網膜 / 血管内皮 / 細胞死
Outline of Final Research Achievements	Macular edema is caused by retinal fluid, and causes an retinal neuronal cell disorder, eventually causing irreversible retinal degeneration. Experiments were conducted to elucidate the mechanism of retinal cell degeneration after the macular edema. Immunohistochemistry confirmed the expression of the P2x7 receptor on the cultured cells. The adenosine three phosphate (ADENOSINE TRIPHOSPHATE; ATP) causes cell death. Serum and ATP were added to the culture to confirm cell death. ATP was injected into mouse eyes, and retinal cell death and retinal degeneration was observed. When ATP and BBG were simultaneously administered to the mouse eyes, it was found that retinal neuronal cell death could be suppressed compared to control. The BBG, which we developed as an surgical agent, could suppress neural cell death associated with retinal edema. These results showed that extracellular ATP can cause macula retinal cells, and cause macular degeneration, and become a potential treatment target.
Free Research Field	眼科学
Academic Significance and Societal Importance of the Research Achievements	黄斑浮腫にはATPを介した網膜神経細胞死が重要な役割を果たし、網膜変性から視力障害を起こすことが示された。我々が手術補助剤として開発したBrillinat Blue Gには内境界膜染色作用以外にも網膜浮腫に伴う神経細胞死を抑制しうることが証明された。BBGは米国FDAでも眼科手術時に内境界膜剥離に使用する剤として認可をうけた。このように培養細胞および動物モデルを用いて、細胞外ATPが黄斑の網膜細胞し、黄斑変性を引き起こし、今後治療標的となり得る可能性を示すことができた。