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Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer

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Listed:
  • Eun Jung Lee

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST)
    Celliaz Ltd.)

  • Museong Kim

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Sooyeon Park

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST)
    Celliaz Ltd.)

  • Ji Hyeon Shim

    (Celliaz Ltd.)

  • Hyun-Ju Cho

    (Korea Research Institute of Bioscience and Biotechnology
    University of Science and Technology)

  • Jung Ah Park

    (Celliaz Ltd.)

  • Kihyun Park

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Dongeun Lee

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Jeong Hwan Kim

    (Korea Research Institute of Bioscience and Biotechnology)

  • Haeun Jeong

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Fumio Matsuzaki

    (RIKEN Centre for Biosystems Dynamics Research
    Kyoto University)

  • Seon-Young Kim

    (Korea Research Institute of Bioscience and Biotechnology)

  • Jaehoon Kim

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Hanseul Yang

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Jeong-Soo Lee

    (Korea Research Institute of Bioscience and Biotechnology
    University of Science and Technology)

  • Jin Woo Kim

    (Korea Advanced Institute of Science and Technology (KAIST)
    Korea Advanced Institute of Science and Technology (KAIST)
    Celliaz Ltd.)

Abstract

Individuals with retinal degenerative diseases struggle to restore vision due to the inability to regenerate retinal cells. Unlike cold-blooded vertebrates, mammals lack Müller glia (MG)-mediated retinal regeneration, indicating the limited regenerative capacity of mammalian MG. Here, we identify prospero-related homeobox 1 (Prox1) as a key factor restricting this process. Prox1 accumulates in MG of degenerating human and mouse retinas but not in regenerating zebrafish. In mice, Prox1 in MG originates from neighboring retinal neurons via intercellular transfer. Blocking this transfer enables MG reprogramming into retinal progenitor cells in injured mouse retinas. Moreover, adeno-associated viral delivery of an anti-Prox1 antibody, which sequesters extracellular Prox1, promotes retinal neuron regeneration and delays vision loss in a retinitis pigmentosa model. These findings establish Prox1 as a barrier to MG-mediated regeneration and highlight anti-Prox1 therapy as a promising strategy for restoring retinal regeneration in mammals.

Suggested Citation

  • Eun Jung Lee & Museong Kim & Sooyeon Park & Ji Hyeon Shim & Hyun-Ju Cho & Jung Ah Park & Kihyun Park & Dongeun Lee & Jeong Hwan Kim & Haeun Jeong & Fumio Matsuzaki & Seon-Young Kim & Jaehoon Kim & Han, 2025. "Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58290-8
    DOI: 10.1038/s41467-025-58290-8
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    References listed on IDEAS

    as
    1. James M. Wells & Fiona M. Watt, 2018. "Diverse mechanisms for endogenous regeneration and repair in mammalian organs," Nature, Nature, vol. 557(7705), pages 322-328, May.
    2. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    3. Nikolas L. Jorstad & Matthew S. Wilken & William N. Grimes & Stefanie G. Wohl & Leah S. VandenBosch & Takeshi Yoshimatsu & Rachel O. Wong & Fred Rieke & Thomas A. Reh, 2017. "Stimulation of functional neuronal regeneration from Müller glia in adult mice," Nature, Nature, vol. 548(7665), pages 103-107, August.
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