Roles of glial endoplasmic reticulum stress response in the pathophysiology of glaucoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kanazawa University
• Principal Investigator: Takarada-Iemata Mika 金沢大学, 医学系, 助教 (40565412)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 網膜 / 神経変性 / ミュラーグリア / 視神経障害 / 小胞体ストレス応答 / 神経栄養因子

Outline of Final Research Achievements

Glaucoma causes vision loss due to progressive degeneration of retinal ganglion cells, but its pathological basis remains unclear. Glaucoma is considered as a neurodegenerative disease and endoplasmic reticulum stress response has been known as important regulator of neurodegenerative diseases. We focused on the ATF6 pathway, one of the three major axes of endoplasmic reticulum stress response, and elucidated its importance and molecular mechanisms in retinal neurodegeneration. Our results suggest that the ATF6 pathway induced after optic nerve injury plays a neuroprotective role by regulating glial cell function rather than retinal ganglion cells.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患研究において、元来、小胞体ストレス応答は神経細胞における重要性が注目されていた。本研究は、小胞体ストレス応答がグリア細胞の機能に寄与することで神経変性を制御することおよびその分子機構の一端を明らかにした。小胞体ストレスの制御は種々の神経変性疾患において重要であり、本研究で得られた成果は、緑内障をはじめとする神経変性疾患の治療法開発において基盤となる知見の蓄積に貢献すると考えられる。