PUBLICATION

A comparative analysis of gene and protein expression in chronic and acute models of photoreceptor degeneration in adult zebrafish

Authors
Kramer, A.C., Carthage, J., Berry, Y., Gurdziel, K., Cook, T.A., Thummel, R.
ID
ZDB-PUB-231002-99
Date
2023
Source
Frontiers in cell and developmental biology   11: 12332691233269 (Journal)
Registered Authors
Thummel, Ryan
Keywords
3′mRNA-seq, Müller glia, chronic light, microglia, photoreceptor degeneration, rod precursor, stem cell, zebrafish
Datasets
GEO:GSE233896
MeSH Terms
none
PubMed
37745292 Full text @ Front Cell Dev Biol
Abstract
Background: Adult zebrafish are capable of photoreceptor (PR) regeneration following acute phototoxic lesion (AL). We developed a chronic low light (CLL) exposure model that more accurately reflects chronic PR degeneration observed in many human retinal diseases. Methods: Here, we characterize the morphological and transcriptomic changes associated with acute and chronic models of PR degeneration at 8 time-points over a 28-day window using immunohistochemistry and 3'mRNA-seq. Results: We first observed a differential sensitivity of rod and cone PRs to CLL. Next, we found no evidence for Müller glia (MG) gliosis or regenerative cell-cycle re-entry in the CLL model, which is in contrast to the robust gliosis and proliferative response from resident MG in the AL model. Differential responses of microglia between the models was also observed. Transcriptomic comparisons between the models revealed gene-specific networks of PR regeneration and degeneration, including genes that are activated under conditions of chronic PR stress. Finally, we showed that CLL is at least partially reversible, allowing for rod and cone outer segment outgrowth and replacement of rod cell nuclei via an apparent upregulation of the existing rod neurogenesis mechanism. Discussion: Collectively, these data provide a direct comparison of the morphological and transcriptomic PR degeneration and regeneration models in zebrafish.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping