Analysis of intra-ocular inflammation during retinal photoreceptor degeneration

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09693
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Sumiko 東京大学, 医学部附属病院, 届出研究員 (60240735)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 網膜 / マウス / 変性 / 炎症

Outline of Final Research Achievements

Inflammation is considered to contribute to the initiation and development of retina. Activation of immune-competent cells such as microglia are reported to be activated in the retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma. We had previously found that mouse microglia expressing v-RAS showed different activation state, suggesting that different micro-environment of inflammation in the retina contributes to differential state of activation of the microglia. Our question in this work is whether heterogeneity of inflammation present in the retina or not. By using frozen sections of the mouse retina and laser-micro dissection machine, we vertically cut out healthy and degenerating retina to 3 parts, and each part was served to proteome analysis. We identified retinal layer-specific protein expression patterns in each layer, and the patterns change with progression of retinal degeneration.

Free Research Field

網膜発生、疾患分子基盤

Academic Significance and Societal Importance of the Research Achievements

視細胞変性症は、糖尿病性網膜症、加齢黄斑変性症、網膜色素変性症などいずれも発症は加齢と強く関係し、この背景として、眼内での炎症サーキットの活性化が想定されるがその実体と分子機序、さらになぜ視細胞が選択的に変性していくのかは不明である。本研究により、網膜内で不均一な炎症像が観察されることが示され、炎症制御を時間軸とともに、空間的にも捉えて、標的を明確にして行う戦略につながる重要な手掛かりとなった。また、組織の切片を切り出してタンパク質を網羅的に同定する手法は、サンプル調整に高度な機器や技術も不要で汎用性が高いものである。