Neuroinflammation as a cause of differential Müller cell regenerative responses to retinal injury
Unlike mammals, some nonmammalian species recruit Müller glia for retinal regeneration after injury. Identifying the underlying mechanisms may help to foresee regenerative medicine strategies. Using a <i>Xenopus</i> model of retinitis pigmentosa, we found that Müller cells actively proliferate upon photoreceptor degeneration in old tadpoles but not in younger ones. Differences in the inflammatory microenvironment emerged as an explanation for such stage dependency. Functional analyses revealed that enhancing neuroinflammation is sufficient to trigger Müller cell proliferation, not only in young tadpoles but also in mice. In addition, we showed that microglia are absolutely required for the response of mouse Müller cells to mitogenic factors while negatively affecting their neurogenic potential. However, both cell cycle reentry and neurogenic gene expression are allowed when applying sequential pro- and anti-inflammatory treatments. This reveals that inflammation benefits Müller glia proliferation in both regenerative and nonregenerative vertebrates and highlights the importance of sequential inflammatory modulation to create a regenerative permissive microenvironment.
Authors
- Patrick Pla (ORCID: https://orcid.org/0000-0002-5957-2340)
- Albert Chesneau
- Juliette Bitard (ORCID: https://orcid.org/0000-0001-6626-3522)
- Jérôme E. Roger (ORCID: https://orcid.org/0000-0002-5061-230X)
- Karine Parain
- Muriel Perron (ORCID: https://orcid.org/0000-0002-1558-8236)
- Xavier Sánchez‐Sáez (ORCID: https://orcid.org/0000-0001-5128-0979)
- Sophie Lourdel
- Yann Audic (ORCID: https://orcid.org/0000-0003-2498-9792)
- Diana García-García (ORCID: https://orcid.org/0000-0003-1681-6074)
- Caroline Borday (ORCID: https://orcid.org/0000-0001-8531-409X)
- Lorena Vidal‐Gil (ORCID: https://orcid.org/0000-0002-2984-5280)
- Alicia Donval (ORCID: https://orcid.org/0009-0006-1822-539X)
- Odile Bronchain (ORCID: https://orcid.org/0000-0001-8932-8907)
- Morgane Locker (ORCID: https://orcid.org/0000-0001-5256-9440)
- Despoina Kazani
- Julien Ricard (ORCID: https://orcid.org/0000-0002-6983-5087)
- Solène Pottin
- Léa Siron
- Demi Van Westendorp (ORCID: https://orcid.org/0000-0002-1637-3747)
- Jingxian Lun
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Paris-Saclay (FR)
- Institut des Neurosciences Paris-Saclay (FR)
- Institut de génétique et de développement de Rennes (FR)
- Université de Rennes (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1126/sciadv.adp7916
- Citations
- 13
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- Infrastructures en Biologie Santé et Agronomie