PUBLICATION
Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina
- Authors
- Gharbi, N., Røise, D., Førre, J.E., Edson, A.J., Hushagen, H.A., Tronci, V., Frøyset, A.K., Fladmark, K.E.
- ID
- ZDB-PUB-211230-3
- Date
- 2021
- Source
- Antioxidants (Basel, Switzerland) 10(12): (Journal)
- Registered Authors
- Edson, Amanda, Fladmark, Kari E., Hushagen, Helena
- Keywords
- DJ-1, Müller cell, neurodegeneration, oxidative stress, retina
- MeSH Terms
- none
- PubMed
- 34942966 Full text @ Antioxidants (Basel)
Citation
Gharbi, N., Røise, D., Førre, J.E., Edson, A.J., Hushagen, H.A., Tronci, V., Frøyset, A.K., Fladmark, K.E. (2021) Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina. Antioxidants (Basel, Switzerland). 10(12):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping