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Yvan Arsenijevic, Sarah Decembrini; Conversion of Photoreceptors into Glast-Positive Progenitor Cells during Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1255.
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© ARVO (1962-2015); The Authors (2016-present)
Several studies investigated whether Muller glial (MG) cells of the retina have a regenerative potential to replace lost photoreceptors during retinal degeneration. In Zebrafish, MG cells can replace degenerating photoreceptors, whereas in mouse some MG cells start a dedifferentiation program but do not complete the acquisition of a photoreceptor fate. To date, few and unconfirmed studies addressed the photoreceptor behavior during retinal degeneration.
To that aim, we crossed the Crx-GFP with the Glast-DsRed mouse lines expressing the green and red reporter genes in post-mitotic photoreceptors and in adult MG cells respectively. Time-lapse video , cell sorting, RT-PCR and immunohistochemical studies were performed.
We notably observed that during retinal development the Glast transgene is expressed in retinal progenitors starting from embryonic day (E) 14, attested by RT-PCR analysis of a sorted Glast-positive population. Cell sorting study revealed the presence of double positive cells showing that some Glast-positive cells generate photoreceptors. Photoreceptor degeneration was induced by injecting the neurotoxic MNU compound in 2 month old mice. Retinas of treated mice were collected after 1 day of treatment and embedded in culture to follow the expression of Crx and Glast transgenes by time lapse video. Using a fully automated cell tracking software, we traced migrating green and red fluorescent cells in time and space up to 2 days. Surprisingly, we observed that after treatment several displaced cells expressing GFP (post-mitotic photoreceptors) started translating the Glast-DsRed transgene. FACS analysis revealed that a low percentage of Crx-Glast-positive cells are in S-phase.
So far, research focused prominently on the transition of glia towards a neuronal fate during retinal degeneration and little attention was reported on photoreceptor behavior. The present data depict a new situation in which photoreceptors lose their specific identity and start expressing progenitor-like markers in the attempt to re-enter the cell cycle rendering the interpretation of regeneration, in certain situation, challenging. This cell conversion needs also to be analyzed in light of our recent data demonstrating the important role of cell cycle proteins during the photoreceptor death process.
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