Novel treatment for diabetic macular edema not dependent on anti-VEGF therapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16997
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Arima Mitsuru 九州大学, 大学病院, 助教 (60772845)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 糖尿病黄斑浮腫 / 血液網膜関門 / 密着結合

Outline of Final Research Achievements

Although intravitreal injection of anti-vascular endothelial growth factor antibody (anti-VEGF therapy) is performed for diabetic macular edema (DME), it is ineffective in about 40% of patients. Therefore, we attempted to develop a novel therapy not dependent on anti-VEGF therapy. In vivo experiments using DME model mice revealed that ROCK activated in DME retina promotes retinal vascular hyperpermeability. To identify the association of ROCK with DME formation in ditail, we also conducted in vitro experiments using cultured endothelial cells. Finally, we demonstrated 1) ROCK is an upstream molecule controlling retinal inflammation, and 2) ROCK acts as a downstream molecule of various inflammatory cytokines as well as VEGF and promotes the disruption of tight junction assembly between vascular endothelial cells. Our results suggested that ROCK inhibition may be superior to anti-VEGF therapy.

Free Research Field

網膜硝子体

Academic Significance and Societal Importance of the Research Achievements

現在糖尿病黄斑浮腫(DME)に対する第一治療選択肢は抗血管内皮増殖因子抗体の硝子体注射(抗VEGF治療)であるが、複数年継続加療を行っても約4割の患者で効果がない。つまり抗VEGF療法に依存しない治療法の開発が急務である。本研究成果により、ROCK阻害療法が抗VEGF療法に優る治療効果を有する可能性が示唆された。抗VEGF療法抵抗性DMEは本邦だけでも十数万人存在しており、これらの患者の視機能改善を達成すべく現在国内企業とともにROCK阻害剤の臨床応用に着手している。