Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa
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- Funatsu, Jun
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Murakami, Yusuke
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Shimokawa, Shotaro
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Nakatake, Shunji
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Fujiwara, Kohta
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Okita, Ayako
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Fukushima, Masatoshi
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Shibata, Kensuke
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Department of Genomics and Molecular Analysis, Yamaguchi University School of Medicine
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- Yoshida, Noriko
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Clinical Research Center, Saga University Hospital
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- Koyanagi, Yoshito
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- 秋山, 雅人
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Department of Ocular Pathology and Imaging Science, Graduate School of Medical Science, Kyushu University
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- 納富, 昭司
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Nakao, Shintaro
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Hisatomi, Toshio
- Department of Ophthalmology, Chikushi Hospital, Fukuoka University
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- 武田, 篤信
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Paschalis, Eleftherios I
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston Keratoprosthesis Laboratory, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary,Harvard Medical School Disruptive Technology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary,Harvard Medical School
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- Vavvas, Demetrios G
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Angiogenesis Laboratory, Department of Ophthalmology, MassachusettsEye and Ear Infirmary,Harvard Medical School
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- Ikeda, Yasuhiro
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Department of Ophthalmology, Faculty of Medicine, University of Miyazaki
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- Sonoda, Koh-Hei
- Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
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- Karen E Nelson
- editor
説明
Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s)— tissue-resident microglia and/or peripheral monocyte-derived macrophages (mφ)— are implicated in the progression of the disease. Here, we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mφ by Ccl2 deficiency or immune modulation via intravenous nanoparticle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.
収録刊行物
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- PNAS Nexus
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PNAS Nexus 1 (1), 1-14, 2022-03
Oxford University Press
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詳細情報 詳細情報について
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- CRID
- 1050021615576532736
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- ISSN
- 27526542
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- HANDLE
- 2324/7161943
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- PubMed
- 35529318
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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