Elucidation of mechanism of the retina ganglion cell death against aldosterone neurotoxicity

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hiroshima University (2018-2019); Kagawa University (2017)
• Principal Investigator: Hirooka Kazuyuki 広島大学, 病院(医), 准教授 (10325350)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 緑内障 / 網膜神経節細胞 / アルドステロン

Outline of Final Research Achievements

We reported that the renin-angiotensin-aldosterone system (RAAS) appeared to play an important role with regard to the neuronal degeneration that occured in the retina. Glutamate excitotoxicity triggered by overactivation of the N-methyl-D-aspartate (NMDA) receptors may be a potential risk factor for retinal ganglion cell (RGC) death. Our findings show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.
We investigated the relationship between the plasma concentration of aldosterone and changes in the number of RGCs after systemic administration of aldosterone. There was a negative correlation between the plasma aldosterone concentration and the number of RGCs. Systemic administration of aldosterone caused a decrease in optic nerve head blood flow. Although the blood flow decrease was well correlated with RGC loss, the mild blood flow reduction indicates that retinal ischemia was unlikely to be the primary cause of RGC loss.

Free Research Field

緑内障

Academic Significance and Societal Importance of the Research Achievements

緑内障では網膜神経節細胞が障害されるが、この細胞死をもたらす経路を明らかにすることが、緑内障治療において重要である。我々は網膜神経節細胞死を引き起こす新しいメカニズムを明らかにした。さらに血液中のアルドステロンの濃度が高いほど、より多くの網膜神経節細胞が障害を受けることを今回明らかにしたが、これは従来から我々が報告してきたアルドステロンが網膜神経節細胞死を引き起こすことを一層明白にしたものである。今回の研究でアルドステロンによる網膜神経節細胞死のメカニズムが明らかになってきたことから、将来の治療法の開発に繋がり、結果として緑内障による失明を減らすことができるものと思われる。