2022 Fiscal Year Final Research Report
Development of a disease model of hereditary retinal degeneration caused by abnormal RNA metabolism and elucidation of the pathogenic mechanism
Project/Area Number |
20K18348
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56060:Ophthalmology-related
|
Research Institution | Oita University |
Principal Investigator |
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | ゼブラフィッシュ / 神経変性疾患 / 網膜 / RNAエキソソーム / 背地適応 |
Outline of Final Research Achievements |
RNA exosomes play an important role in RNA quality control. The principal investigator developed an animal model zebrafish model of the disease in which the exosc2 gene was Knockout, and reported that the pathology was associated with an abnormal nucleotide metabolic balance. The animal model showed decreased retinal rhodopsin in rhodopsin immunostaining. The retinal function of the model animal was confirmed to be decreased by examination of electroretinograms and back-ground adaptation. These results suggest that genetic abnormalities in RNA exosomes are associated with abnormal nucleotide metabolic balance and may cause neurodegenerative diseases, including retinal degeneration.
|
Free Research Field |
眼科学
|
Academic Significance and Societal Importance of the Research Achievements |
RNAエキソソームは、RNAの品質管理に重要な役割を担っている。このRNAエキソソームを構成するEXOSC2の遺伝子変異は、網膜変性を含む神経変性疾患の原因となることが報告されているが、その詳細な病態メカニズムは解明されていない。研究代表者らは、exosc2遺伝子をKnockoutした疾患動物モデルゼブラフィッシュを作製し、その病態にヌクレオチド代謝バランスの異常が関連し、網膜電図検査、背地適応の検討などの実験を通して、RNAエキソソームの異常が網膜変性の原因となる可能性があることを報告した。この研究成果はRNAエキソソーム関連神経変性疾患の病態解明、ひいては治療法の確立に繋がる可能性がある。
|