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.
Si ChenKira L LathropTakaaki KuwajimaJeffrey M GrossPublished in: Development (Cambridge, England) (2021)
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, such as glaucoma, and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities. 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.
Keyphrases
- optic nerve
- rna seq
- single cell
- optical coherence tomography
- immune response
- innate immune
- inflammatory response
- stem cells
- cell therapy
- induced apoptosis
- cerebral ischemia
- mesenchymal stem cells
- neuropathic pain
- healthcare
- genome wide
- gene expression
- lps induced
- big data
- subarachnoid hemorrhage
- tissue engineering
- artificial intelligence
- dendritic cells
- health information
- bioinformatics analysis
- drug administration