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XB-ART-60529
Glia 2024 Apr 01;724:759-776. doi: 10.1002/glia.24502.
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Regeneration from three cellular sources and ectopic mini-retina formation upon neurotoxic retinal degeneration in Xenopus.

Parain K , Chesneau A , Locker M , Borday C , Perron M .


Abstract
Regenerative abilities are not evenly distributed across the animal kingdom. The underlying modalities are also highly variable. Retinal repair can involve the mobilization of different cellular sources, including ciliary marginal zone (CMZ) stem cells, the retinal pigmented epithelium (RPE), or Müller glia. To investigate whether the magnitude of retinal damage influences the regeneration modality of the Xenopus retina, we developed a model based on cobalt chloride (CoCl2 ) intraocular injection, allowing for a dose-dependent control of cell death extent. Analyses in Xenopus laevis revealed that limited CoCl2 -mediated neurotoxicity only triggers cone loss and results in a few Müller cells reentering the cell cycle. Severe CoCl2 -induced retinal degeneration not only potentializes Müller cell proliferation but also enhances CMZ activity and unexpectedly triggers RPE reprogramming. Surprisingly, reprogrammed RPE self-organizes into an ectopic mini-retina-like structure laid on top of the original retina. It is thus likely that the injury paradigm determines the awakening of different stem-like cell populations. We further show that these cellular sources exhibit distinct neurogenic capacities without any bias towards lost cells. This is particularly striking for Müller glia, which regenerates several types of neurons, but not cones, the most affected cell type. Finally, we found that X. tropicalis also has the ability to recruit Müller cells and reprogram its RPE following CoCl2 -induced damage, whereas only CMZ involvement was reported in previously examined degenerative models. Altogether, these findings highlight the critical role of the injury paradigm and reveal that three cellular sources can be reactivated in the very same degenerative model.

PubMed ID: 38225726
Article link: Glia
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: mpi opn1lw opn1sw otx2 pax6 pcna rho rpe rpe65 sox9 vim yap1
GO keywords: cell proliferation [+]
Antibodies: BrdU Ab10 BrdU Ab12 Glul Ab2 M-Opsin Ab1 Otx2 Ab5 Pax6 Ab5 Pcna Ab1 Rho Ab1 S-Opsin Ab1 Sox9 Ab4 Yap1 Ab6


Article Images: [+] show captions