Investigation of the chronic inflammatory mechanisms and development of a new therapeutic strategy in Retinitis Pigmentosa

2016 Fiscal Year Final Research Report

• Project/Area Number: 26861455
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Yoshida Noriko 九州大学, 医学研究院, 共同研究員 (70725853)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 慢性炎症

Outline of Final Research Achievements

Microglial activation and the consequent chronic inflammation have been implicated in the pathogenesis of Retinitis Pigmentosa (RP). Microglial cells differentiate into "pro-inflammatory (M1)" or "anti-inflammatory (M2)" subsets depending on surrounding microenviromental factors. In this study, we investigated the level and localization of each microglial subset in the degenerating retina, using rd10 mice, a mouse model of RP. We found that the level of M1 markers was significantly　increased compared to M2 markers in the retina of rd10 mice, and the level of each macrophage markers was gradually decreased during retinal degeneration. Furthermore, we investigated the neuroprotective effect of statin that promotes the microglial differentiation into M2 phenotype.

Free Research Field

網膜

Academic Significance and Societal Importance of the Research Achievements

網膜色素変性（RP）は有効な治療法が確立されていない遺伝性の網膜変性疾患である。我々は、原因遺伝子に依存しないRPに共通した病態として、慢性炎症の網膜変性への関与を報告してきた。本研究では、RPモデルマウス網膜では炎症促進型マクロファージが活性化しており、網膜変性早期における網膜の慢性炎症の誘導に関与している可能性を明らかにした。また、抗炎症作用などの多面的効果を有するピタバスタチンをRPモデルマウスに投与して網膜マクロファージ活性化の抑制や視細胞保護効果を検証し、新たな治療薬としての可能性を確認した。