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

• 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
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 慢性炎症 / 医療・福祉

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.

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。

Research Products

• [Journal Article] MUTYH promotes oxidative microglial activation and inherited retinal degeneration. (2016)
  • Author(s): Nakatake S, Murakami Y, Ikeda Y, Morioka N, Tachibana T, Fujiwara K, Yoshida N, Notomi S, Hisatomi T, Yoshida S, Ishibashi T, Nakabeppu Y, Sonoda KH.
  • Journal Title: JCI Insight. Volume: 1(15)
  • Peer Reviewed
• [Journal Article] Association Between Aqueous Flare and Epiretinal Membrane in Retinitis Pigmentosa. (2016)
  • Author(s): Fujiwara K, Ikeda Y, Murakami Y, Nakatake S, Tachibana T, Yoshida N, Nakao S, Hisatomi T, Yoshida S, Yoshitomi T, Sonoda KH, Ishibashi T.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 57(10) Pages: 4282-6
  • Peer Reviewed
• [Journal Article] Vitreous cysts in patients with retinitis pigmentosa. (2015)
  • Author(s): Yoshida N, Ikeda Y, Murakami Y, Nakatake S, Tachibana T, Notomi S, Hisatomi T, Ishibashi T.
  • Journal Title: Jpn J Ophthalmol. Volume: 59(6) Pages: 373-7
  • Peer Reviewed
• [Journal Article] Factors affecting visual acuity after cataract surgery in patients with retinitis pigmentosa. (2015)
  • Author(s): Yoshida N, Ikeda Y, Murakami Y, Nakatake S, Fujiwara K, Notomi S, Hisatomi T, Ishibashi T
  • Journal Title: Ophthalmology. Volume: 122(5) Pages: 903-8
  • Peer Reviewed
• [Journal Article] Long-term Surgical Outcomes of Epiretinal Membrane in Patients with Retinitis Pigmentosa. (2015)
  • Author(s): Ikeda Y, Yoshida N, Murakami Y, Nakatake S, Notomi S, Hisatomi T, Enaida H, Ishibashi T.
  • Journal Title: Sci Rep. Volume: 5 Pages: 13078-13078
  • Peer Reviewed
• [Journal Article] Correlation between macular blood flow and central visual sensitivity in retinitis pigmentosa. (2015)
  • Author(s): Murakami Y, Ikeda Y, Akiyama M, Fujiwara K, Yoshida N, Nakatake S, Notomi S, Nabeshima T, Hisatomi T, Enaida H, Ishibashi T.
  • Journal Title: Acta Ophthalmol. Volume: 93(8)
  • Peer Reviewed
• [Journal Article] Relationship between aqueous flare and visual function in retinitis pigmentosa. (2015)
  • Author(s): Murakami Y, Yoshida N, Ikeda Y, Nakatake S, Fujiwara K, Notomi S, Nabeshima T, Nakao S, Hisatomi T, Enaida H, Ishibashi T.
  • Journal Title: Am J Ophthalmol. Volume: 159(5)
  • Peer Reviewed
• [Journal Article] Factors Affecting Visual Acuity after Cataract Surgery in Patients with Retinitis Pigmentosa. (2015)
  • Author(s): Yoshida N, Ikeda Y, Murakami Y, Nakatake S, Fujiwara K, Notomi S, Hisatomi T, Ishibashi T.
  • Journal Title: Ophthalmology. Volume: 122(5) Pages: 903-8
  • Peer Reviewed / Open Access
• [Journal Article] Relationship Between Aqueous Flare and Visual Function in Retinitis Pigmentosa. (2015)
  • Author(s): Murakami Y, Yoshida N, Ikeda Y, Nakatake S, Fujiwara K, Notomi S, Nabeshima T, Nakao S, Hisatomi T, Enaida H, Ishibashi T.
  • Journal Title: Am J Ophthalmol. Volume: 159(5) Pages: 958-963
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic efficacy of topical unoprostone isopropyl in retinitis pigmentosa. (2014)
  • Author(s): Akiyama M, Ikeda Y, Yoshida N, Notomi S, Murakami Y, Hisatomi T, Enaida H, Ishibashi T.
  • Journal Title: Acta Ophthalmol. Volume: 92(3)
  • Peer Reviewed / Open Access
• [Presentation] 網膜色素変性への炎症の関与と将来の治療 (2014)
  • Author(s): 吉田倫子
  • Organizer: 第68回日本臨床眼科学会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] 1.Relationship between Aqueous Flare and Visual Function in Retinitis Pigmentosa. (2014)
  • Author(s): Noriko Yoshida, Yasuhiro Ikeda, Yusuke Murakami, Shunji Nakatake, Kota Fujiwara, Shoji Notomi, Shintaro Nakao, Toshio Hisatomi, Hiroshi Enaida, and Tatsuro Ishibashi
  • Organizer: ARVO.
  • Place of Presentation: オーランド、米国
  • Year and Date: 2014-05-04 – 2014-05-08
• [Book] 網膜変性疾患診療のすべて (2016)
  • Author(s): 村上晶・吉村長久
  • Publisher: 医学書院