Reintroduction of dj-1 in müller cells inhibits retinal degeneration in the dj-1 deficient retina
Gharbi, Naouel; Røise, Dagne; Førre, Jorunn-Elise; Edson, Amanda Jayne; Hushagen, Helena Amalie; Tronci, Valentina; Frøyset, Ann-Kristin; Fladmark, Kari E.
Journal article, Peer reviewed
Published version
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https://hdl.handle.net/11250/2990970Utgivelsesdato
2021Metadata
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- Department of Biological Sciences [2235]
- Registrations from Cristin [9791]
Sammendrag
The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress.