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Nat. Commun., Published: 25 March 2025 | https://doi.org/10.1038/s41467-025-58290-8
Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer
Eun Jung Lee1,2,3,9, Museong Kim1,2,9, Sooyeon Park1,2,3, Ji Hyeon Shim3, Hyun-Ju Cho4,5, Jung Ah Park3, Kihyun Park1, Dongeun Lee1,2, Jeong Hwan Kim6, Haeun Jeong1,2, Fumio Matsuzaki7,8, Seon-Young Kim6, Jaehoon Kim1, Hanseul Yang1,2, Jeong-Soo Lee4,5 & Jin Woo Kim1,2,3
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
2KAIST Stem Cell Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
3Celliaz Ltd., Daejeon, South Korea.
4Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
5KRIBB School, University of Science and Technology, Daejeon, South Korea.
6Korea Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
7Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
8Present address: Department of Aging Science and Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
9These authors contributed equally: Eun Jung Lee, Museong Kim.
Corresponding author
Correspondence to Jin Woo Kim.
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
2KAIST Stem Cell Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
3Celliaz Ltd., Daejeon, South Korea.
4Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
5KRIBB School, University of Science and Technology, Daejeon, South Korea.
6Korea Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
7Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo, Japan.
8Present address: Department of Aging Science and Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
9These authors contributed equally: Eun Jung Lee, Museong Kim.
Corresponding author
Correspondence to Jin Woo Kim.
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.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-26)
- 국내(교신)+국외 연구진
- 생명과학 > 신경생물학
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