Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa

  • Funatsu, Jun
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Murakami, Yusuke
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Shimokawa, Shotaro
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Nakatake, Shunji
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Fujiwara, Kohta
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Okita, Ayako
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Fukushima, Masatoshi
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Shibata, Kensuke
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Department of Genomics and Molecular Analysis, Yamaguchi University School of Medicine
  • Yoshida, Noriko
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Clinical Research Center, Saga University Hospital
  • Koyanagi, Yoshito
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • 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
  • 納富, 昭司
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Nakao, Shintaro
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • Hisatomi, Toshio
    Department of Ophthalmology, Chikushi Hospital, Fukuoka University
  • 武田, 篤信
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University
  • 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
  • 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
  • Ikeda, Yasuhiro
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University Department of Ophthalmology, Faculty of Medicine, University of Miyazaki
  • Sonoda, Koh-Hei
    Department of Ophthalmology, Graduate School of Medical Science, Kyushu University

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

  • PNAS Nexus

    PNAS Nexus 1 (1), 1-14, 2022-03

    Oxford University Press

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