PUBLICATION
Iron contributes to photoreceptor degeneration and Müller glia proliferation in the zebrafish light-treated retina
- Authors
- Boyd, P., Hyde, D.R.
- ID
- ZDB-PUB-220126-42
- Date
- 2022
- Source
- Experimental Eye Research 216: 108947 (Journal)
- Registered Authors
- Hyde, David R.
- Keywords
- Iron, Müller glia, Regeneration, Retina, Transferrin receptor, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis
- Cell Proliferation/drug effects*
- Deferiprone/pharmacology
- Ependymoglial Cells/drug effects*
- Ependymoglial Cells/metabolism
- Ferrous Compounds/toxicity*
- In Situ Nick-End Labeling
- Intravitreal Injections
- Light
- Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism
- Photoreceptor Cells/drug effects*
- Photoreceptor Cells/radiation effects
- Radiation Injuries, Experimental/etiology*
- Radiation Injuries, Experimental/metabolism
- Receptors, Transferrin/metabolism
- Retinal Degeneration/chemically induced*
- Retinal Degeneration/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 35074344 Full text @ Exp. Eye. Res.
Citation
Boyd, P., Hyde, D.R. (2022) Iron contributes to photoreceptor degeneration and Müller glia proliferation in the zebrafish light-treated retina. Experimental Eye Research. 216:108947.
Abstract
Zebrafish possess the ability to completely regenerate the retina following injury, however little is understood about the damage signals that contribute to inducing Müller glia reprogramming and proliferation to regenerate lost neurons. Multiple studies demonstrated that iron contributes to various retinal injuries, however no link has been shown between iron and zebrafish retinal regeneration. Here we demonstrate that Müller glia exhibit transcriptional changes following injury to regulate iron levels within the retina, allowing for increased iron uptake and decreased export. The response of the zebrafish retina to intravitreal iron injection was then characterized, showing that ferrous, and not ferric, iron induces retinal cell death. Additionally, iron chelation resulted in decreased numbers of TUNEL-positive photoreceptors and fewer proliferating Müller glia. Despite the contribution of iron to retinal cell death, inhibition of ferroptosis did not significantly reduce cell death following light treatment. Finally, we demonstrate that both the anti-ferroptotic protein Glutathione peroxidase 4b and the Transferrin receptor 1b are required for Müller glia proliferation following light damage. Together these findings show that iron contributes to cell death in the light-damaged retina and is essential for inducing the Müller glia regeneration response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping