PUBLICATION
Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish
- Authors
- Fimbel, S.M., Montgomery, J.E., Burket, C.T., and Hyde, D.R.
- ID
- ZDB-PUB-070303-16
- Date
- 2007
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 27(7): 1712-1724 (Journal)
- Registered Authors
- Burket, Christopher, Fimbel, Shane, Hyde, David R., Montgomery, Jacob
- Keywords
- retinal degeneration, retinal regeneration, retinal apoptosis, retinal progenitor, Müller glia, zebrafish
- MeSH Terms
-
- Analysis of Variance
- Animals
- Animals, Genetically Modified
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Blotting, Western/methods
- Dose-Response Relationship, Drug
- ELAV Proteins/metabolism
- ELAV-Like Protein 3
- Enzyme Inhibitors/toxicity*
- Glial Fibrillary Acidic Protein/metabolism
- Green Fluorescent Proteins/genetics
- Immunohistochemistry/methods
- In Situ Nick-End Labeling/methods
- Nerve Tissue Proteins/genetics
- Neuroglia/metabolism
- Neuroglia/pathology
- Ouabain/toxicity*
- Proliferating Cell Nuclear Antigen/metabolism
- Regeneration/physiology*
- Retina/pathology*
- Retinal Ganglion Cells/drug effects*
- Time Factors
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 17301179 Full text @ J. Neurosci.
Citation
Fimbel, S.M., Montgomery, J.E., Burket, C.T., and Hyde, D.R. (2007) Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(7):1712-1724.
Abstract
We examined the regenerative capacity of the adult zebrafish retina by intravitreal injection of a low ouabain concentration to rapidly damage the ganglion cell layer (GCL) and inner nuclear layer (INL) with minimal photoreceptor cell damage. By 24 h after ouabain injection, maximal numbers of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-positive cells were detected in the INL and GCL, with low numbers of TUNEL-positive cells in the outer nuclear layer. Immunolabeling revealed that approximately 85% of the HuC/D-positive amacrine and ganglion cells were lost by 7 d post-ouabain injection (dpi). This ganglion cell loss was consistent with the small, but statistically significant, decrease in the optic nerve diameter. The regeneration response began within 1 dpi with increased proliferating cell nuclear antigen (PCNA) expression in both the INL and GCL. By 3 dpi, PCNA expression is primarily restricted to the Muller glia. By 5 dpi, most of the PCNA expression was localized to neuronal progenitors expressing the olig2:egfp transgene rather than the Muller glia. By 7 dpi, the neuronal progenitors began committing to the ganglion cell fate based on the coexpression of the atoh7:EGFP transgene and the zn5 antigen. The regeneration of ganglion and amacrine cells continued until 60 dpi, when they reached 75% of their uninjected control number. This demonstrates that inner retinal damage, without extensive photoreceptor damage, is sufficient to induce a regeneration response that is marked by the Muller glial cells reentering the cell cycle to produce neuronal progenitor cells that regenerate INL and ganglion cells in the zebrafish retina.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping