The role of Fas ligand in retinal detachment induced photoreceptor cell death

• Project/Area Number: 15K20248
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Gunma University
• Principal Investigator: Matsumoto Hidetaka 群馬大学, 大学院医学系研究科, 助教 (30420178)
• Project Period (FY): 2015-04-01 – 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 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 網膜剥離 / 視細胞死 / Fasリガンド / 神経保護

Outline of Final Research Achievements

Separation of photoreceptors from underlying retinal pigment epithelium, as seen retinal detachment (RD), causes photoreceptor cell death, resulting in permanent vision loss. In a majority of cases, photoreceptor cell death occurs even if the retina is successfully reattached surgically. Therefore, it is important to define the mechanism(s) of photoreceptor cell death in the detached retina and establish therapeutic targets that prevent photoreceptor loss and the subsequent decrease in visual acuity.
We investigated the role of Fas ligand (FasL) in RD induced photoreceptor cell death using genetically modified mice. Our results showed that FasL induced cell death of photoreceptors following RD. In addition, photoreceptor loss in detached retina was inhibited by a subretinal injection of recombinant soluble FasL. These indicate that treatment targeting FasL could significantly reduce photoreceptor cell loss in patients with RD.

Research Products

• [Int'l Joint Research] Harvard Medical School/Massachusetts Medical School(米国)
• [Int'l Joint Research] Department of Ophthalmology/Massachusetts Eye and Ear Infirmary/Harvard Medical School(米国)
• [Int'l Joint Research] 3Department of Medicine/University of/Massachusetts Medical School(米国)
• [Journal Article] Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium (2015)
  • Author(s): H Matsumoto, Y Murakami, K Kataoka, S Notomi, D Mantopoulos, G Trichonas, JW Miller, MS Gregory, BR Ksander, A Marshak-Rothstein, and DG Vavvas
  • Journal Title: Cell Death and Disease Volume: 6 Issue: 11 Pages: e1986-e1986
  • DOI: 10.1038/cddis.2015.334
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 網膜剥離後の視細胞死と炎症細胞浸潤におけるFasリガンドの役割 (2015)
  • Author(s): 松本英孝、村上祐介、片岡恵子、納富昭司、Miller Joan、Gregory Meredith、Ksander Bruce、Marshak-Rothstein Ann、Vavvas Demetrios、岸章治
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: ロイトン札幌（札幌）
  • Year and Date: 2015-04-16