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タイトル: | Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy |
著者: | Hata, Masayuki https://orcid.org/0000-0002-5248-5762 (unconfirmed) Hata, Maki Dejda, Agnieszka Pilon, Frédérique Diaz-Marin, Roberto Fournier, Frédérik Joyal, Jean-Sebastien Cagnone, Gael Ochi, Yotaro Crespo-Garcia, Sergio Wilson, Ariel M. Sapieha, Przemyslaw |
著者名の別形: | 畑, 匡侑 越智, 陽太郎 |
キーワード: | retina angiogenesis inflammation dexamethasone retinopathy |
発行日: | 24-Dec-2024 |
出版者: | National Academy of Sciences |
誌名: | Proceedings of the National Academy of Sciences (PNAS) |
巻: | 121 |
号: | 52 |
論文番号: | e2411640121 |
抄録: | Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Here, we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that dexamethasone, a broad-spectrum corticosteroid, suppresses initial formation of pathological preretinal neovascularization in early stages of disease, yet blunts reparative inflammation by impairing distinct myeloid cell populations, and hence reduces beneficial vascular remodeling in later stages of disease. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing lysozyme 2 are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered, particularly in stages associated with persistent neovascularization. |
記述: | ステロイドが新生血管病変に与える二面性 --病的血管新生を抑制するが、修復的な血管再構築を損なう--. 京都大学プレスリリース. 2024-12-20. |
著作権等: | Copyright © 2024 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
URI: | http://hdl.handle.net/2433/290939 |
DOI(出版社版): | 10.1073/pnas.2411640121 |
PubMed ID: | 39693344 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2024-12-20-0 |
出現コレクション: | 学術雑誌掲載論文等 |
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