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bioRxiv · 10.1101/2021.04.08.439090

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

Chen, S.·Lathrop, K.·Kuwajima, T.·Gross, J.
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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, our results support a model in which pro-survival signals in RGCs, mediated by JAK/STAT signaling, counteract the activity of innate immune responses to modulate RGC vulnerability and resilience in the zebrafish retina after severe optic nerve damage.

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Chen, S., Lathrop, K., Kuwajima, T., Gross, J.. 2021-04-10. 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. https://doi.org/10.1101/2021.04.08.439090

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