Primate model to study drusen formation and development of therapeutics

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293377
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: IWATA Takeshi 独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 部長 (90374157)
• Co-Investigator(Kenkyū-buntansha): 溝田 淳 帝京大学, 医学部, 教授 (10239262) ; 下澤 律浩 国立研究開発法人医薬基盤・健康・栄養研究所, 霊長類医科学研究センター, 研究員 (50300786)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 医歯薬学 / 外科系臨床医学 / 眼科学 / 眼性化学・分子生物学 / ドルーゼン

Outline of Final Research Achievements

Early onset cynomolgus macaque monkey with macular drusen was characterized to identify disease-causing mutation and pathological change at tissue and cellular level. The affected monkeys with dominant inheritance develop drusen at two years after birth. Whole genome and whole exome analysis were preformed to narrow the disease locus to a small region on chromosome 1. Three candidate genes were identified to cosegregate with macular drusen. The retinal pigment epithelial (RPE) cells in the fovea of affected monkeys were identified to lose the characteristic of the epithelial cells, Epithelial-Mesenchymal Transition-like phenomenon, leading to change of cell morphology, decreased of autophagy and phagocytosis activities. Complement inhibitors were administered to affected monkey to suppress formation of drusen. Potential inhibitors are being developed.

Free Research Field

眼科学