Analysis of pathogenic mechinism of glaucoma based on commonality with Amyotrophic lateral sclerosis

2015 Fiscal Year Final Research Report

• Project/Area Number: 24592622
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Ohtsubo Masafumi 浜松医科大学, 光尖端医学教育研究センター, 助教 (10327653)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 緑内障 / 筋萎縮性側索硬化症 / 異常蛋白蓄積 / オートファジー

Outline of Final Research Achievements

For “the vacuole-like abnormal intracellular structure” (our finding) which is generated when an anion transport protein SLC4A2 is coexpressed with optineurin (OPTN) and “the OPTN granules” which is induced in cultured cells by the glaucomatous OPTN mutation E50K, we analyzed the signaling pathway, formation difference between ALS- and glaucomatous-mutation, and, the cellular localization.
In addition, we found that these phenomena related to the abnormal protein accumulation were suppressed by induction of autophagy. This effect was also observed in case of the intracellular inclusion generated by another ALS-causative gene TARDBP. It was reported that OPTN is detected in the inclusion bodies of ALS patients’ nerve cells caused by SOD1 or TARDBP mutation. It suggested that over-accumulation of abnormal protein or decreasing of autophagy function of OPTN by mutation is possible disease onset mechanism and that inducing autophagy possibly suppresses the onset of ALS and glaucoma.

Free Research Field

分子細胞生物学