Regeneration from three cellular sources and ectopic mini-retina formation upon neurotoxic retinal degeneration inXenopus

Autor: Parain Karine, Albert Chesneau, Morgane Locker, Caroline Borday, Perron Muriel
Rok vydání: 2023
DOI: 10.1101/2023.05.12.540545
Popis: Regenerative abilities are not evenly distributed across the animal kingdom. Interestingly, the underlying modalities are also highly variable, even among closely related species. In fish or amphibians, retinal repair can involve the mobilization of different cellular sources, including stem cells of the ciliary marginal zone (CMZ), retinal pigmented epithelial (RPE) cells, or Müller glia. The mechanisms that trigger the recruitment of one cell type over another remain elusive. To investigate whether the magnitude of retinal damage might influence the regeneration modality of theXenopusretina, we developed a model based on cobalt chloride (CoCl2) intraocular injection, allowing for a dose-dependent control of cell death extent. Analyses inXenopus laevisrevealed that limited CoCl2-mediated neurotoxicity only triggers cone cell loss and results in a few Müller glia cells reentering the cell cycle, without affecting CMZ cell activity or recruiting RPE cells. Conversely, we found that severe CoCl2-induced retinal degeneration not only potentializes the proliferative response of Müller cells, but also enhances CMZ cell proliferation and, unexpectedly triggers an RPE reprogramming event. Although Müller glia could not regenerate cones under these conditions, both CMZ and RPE-derived proliferative cells could. Strikingly, RPE reprogrammed cells self-organized into an ectopic layered 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 exhibiting distinct neurogenic capacities. Besides, we surprisingly found thatXenopus tropicalisalso has the ability to recruit Müller cells and reprogram its RPE following CoCl2-induced damage, whereas only CMZ cell proliferation 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.
Databáze: OpenAIRE