PUBLICATION
Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina
- Authors
- Chen, S., Lathrop, K.L., Kuwajima, T., Gross, J.M.
- ID
- ZDB-PUB-210918-8
- Date
- 2021
- Source
- Development (Cambridge, England) 149(8): (Journal)
- Registered Authors
- Gross, Jeffrey
- Keywords
- Innate immune system, JAK/STAT, Neuroprotection, RGC, Zebrafish
- Datasets
- GEO:GSE171426
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Female
- Immunity, Innate*
- Janus Kinases/genetics
- Janus Kinases/immunology*
- Male
- Optic Nerve Injuries/genetics
- Optic Nerve Injuries/immunology*
- Retinal Ganglion Cells/immunology*
- STAT Transcription Factors/genetics
- STAT Transcription Factors/immunology*
- Signal Transduction/genetics
- Signal Transduction/immunology*
- Zebrafish/genetics
- Zebrafish/immunology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/immunology*
- PubMed
- 34528064 Full text @ Development
Citation
Chen, S., Lathrop, K.L., Kuwajima, T., Gross, J.M. (2021) Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina. Development (Cambridge, England). 149(8):.
Abstract
Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, these data support a model in which crosstalk between macrophages/microglia and RGCs, mediated by Jak/Stat pathway activity, regulates RGC survival after optic nerve injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping