GSE171426
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
The death of retinal ganglion cells(RGC) after the damage on optic nerve as a result of high intraocular pressure is the main reason of the irreversible blindness in glaucoma patients ,and mammals have very limited ability of maintaining the RGCs after optic nerve injury.Zebrafish,however,possess the ability of keep most RGCs from death after optic nerve injury.  The purpose of this study is to determine which gene or pathway mediate the RGC survival mechanism underlying.It is observed JAK/STAT signaling pathway as well as the innate immune response is activated after optic nerve injury(in this study,optic nerve transection).Pharmacological inhibition of JAK/STAT by intravitreal(IV) injection of JAK inhibitor,P6,induced the reduction of RGC survival while both local and systemic immune suppressor application result in the rescue of RGC survival.Moreover,phospho-STAT3(pSTAT3),which is an evidence of STAT3 activation,demonstrated elevation of expression level after ONT,and the trend of pSTAT3 expression change is consistent with the RGC survival rate change .JAK inhibition reduced pSTAT3 expression level and immune suppressor application elevated the pSTAT3 expression level on RGCs.  In summary,these data suggested JAK/STAT signaling pathway crosstalk with innate immune response create a dynamic balance in the mechanism of RGC survival.Interestingly,innate immune response which was used to be considered promoting tissue repair in other studies,proved to be suppressing RGC survival in this study.These data could be used as reference for future direction of neuroprotection in glaucoma treatment. Overall design: RNA-seq from FACS-purified retinal ganglion cells post optic nerve transection and uninjured contralacteral eyes as control at 3 timepoints: 6,12 and 24 hours post injury(hpi). ONT+ for injured samples and ONT- for control