2021 Fiscal Year Final Research Report
Identification of DAMPs Recognition Mechanisms that Regulate Neuroinflammation in Retinitis Pigmentosa
| Project/Area Number |
19K09952
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 網膜色素変性 / 神経炎症 / DAMPs |
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| Outline of Final Research Achievements |
We investigated the mechanisms of neuroinflammation in retinitis pigmentosa (RP), especially focused on the recognition systems of damage-associated molecular patterns (DAMPs) released from dead cells. TLR/Myd88 or CLRs/Card9 was genetically depleted from RP model mice. Phenotype analyses showed accelerated retinal degeneration by Myd88 deficiency, associated with attenuated microglial migration and neurotoxic changes in retinal microenvironment. These results suggest that TLR/Myd88 pathway is essential for DAMPs recognition in RP and that this pathway mediates neuroprotective microglial activation and migration.
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| Free Research Field |
眼科学
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| Academic Significance and Societal Importance of the Research Achievements |
網膜色素変性（RP）は遺伝性の網膜変性疾患で、治療法のない難病である。近年の研究から神経炎症がRP病態に大きく関わっていることが分かってきたが、どのようなメカニズムで神経炎症が誘導されるのか、その役割は何なのかは不明であった。本研究は、TLR/Myd88経路がマイクログリアの活性化と遊走に重要であり、TLR/Myd88を介した神経炎症が網膜保護的に働くことを明らかにした。RPの神経炎症について、そのメカニズムの一端を解明するとともに、TLR/Myd88を新たなRPの治療標的として同定することができた。
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