Development of novel comprehensive molecular therapies for intraocular proliferative diseases targeting periretinal fibrovascular membranes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293374
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Yoshida Shigeo 九州大学, 医学(系)研究科(研究院), 准教授 (50363370)
• Co-Investigator(Kenkyū-buntansha): 石橋 達朗 九州大学, 大学病院, その他 (30150428) ; 中尾 新太郎 九州大学, 大学病院, 助教 (50583027) ; 佐々 由季生 福岡大学, 医学部, 講師 (80580315)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖尿病網膜症 / 加齢黄斑変性 / ペリオスチン / テネイシンC / 眼内増殖 / 分子標的薬 / 核酸医薬

Outline of Final Research Achievements

In intraocular proliferative diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), fibro (vascular) membrane (FVM) formation above and beneath the retina plays a pivotal role in the primary pathology. We have succeeded in extracting approximately 100 highly expressed genes in FVMs associated with PDR, which included periostin and tenascin-C, a matricellular protein.
We showed that the expression of periostin and tenascin-C was increased in the retinas of a mouse model of oxygen-induced retinal neovascularization (NV) and in choroidal NV. A new class of RNA interference (RNAi) agent that targets periostin and tenascin-C had a significant inhibitory effect on the retinal NV, CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between these matricellular proteins and intraocular FVM formation, and a potential therapeutic role of the new intravitreal RNAi agents for DR and AMD.

Free Research Field

眼科学