論文 - 詳細
| RRC ID | 83609 |
|---|---|
| 著者 | Lee EJ, Kim M, Park S, Shim JH, Cho HJ, Park JA, Park K, Lee D, Kim JH, Jeong H, Matsuzaki F, Kim SY, Kim J, Yang H, Lee JS, Kim JW. |
| タイトル | Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 16(1) |
| ページ | 2928 |
| 公開日 | 2025-3-25 |
| DOI | 10.1038/s41467-025-58290-8 |
| PII | 10.1038/s41467-025-58290-8 |
| PMID | 40133314 |
| PMC | PMC11937340 |
| MeSH | Animals Disease Models, Animal Ependymoglial Cells* / metabolism Homeodomain Proteins* / genetics Homeodomain Proteins* / metabolism Humans Mice Mice, Inbred C57BL Nerve Regeneration Neuroglia / metabolism Regeneration Retina* / metabolism Retinal Degeneration / metabolism Retinal Degeneration / pathology Retinal Degeneration / therapy Retinal Neurons / metabolism Tumor Suppressor Proteins* / genetics Tumor Suppressor Proteins* / metabolism Zebrafish* |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 143 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 1.7 |
| リソース情報 | |
| 実験動物マウス | RBRC05565 RBRC05559 |