Neurosteroids modulate the effects of high pressure in a rat ex vivo glaucoma model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10888
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Akita University
• Principal Investigator: Ishikawa Makoto 秋田大学, 医学(系)研究科(研究院), 准教授 (10212854)
• Co-Investigator(Kenkyū-buntansha): 吉冨 健志 秋田大学, 医学(系)研究科(研究院), 教授 (60191623)
• Research Collaborator: TAKASEKI Sanae
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 緑内障 / 眼圧 / グルタミン酸受容体 / GABA受容体 / 神経ステロイド / 神経保護

Outline of Final Research Achievements

In the present study using a rat ex vivo glaucoma model, we found that the synthesis of neurosteroids, allopregnanolone (AlloP) and 24(S)-hydroxycholesterol (24SH), is facilitated by pressure elevation. Moreover, we found that AlloP and 24SH are neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of AlloP and 24SH synthesizing enzymes. LC-MS/MS revealed that AlloP and 24SH levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by high pressure was ameliorated by AlloP and 24SH. We also observed that co-administration of 24SH (0.1 microM) and AlloP (0.1 microM), concentrations that are only partially effective when administered alone, prevents axonal swelling under high pressure. This apparent enhanced protection indicates strong interaction between the two neurosteroids to preserve neuronal integrity.

Free Research Field

緑内障の基礎研究