Purchase this article with an account.
Wei Li, Tantai Zhao, Jingxing Ou, Francisco M Nadal-Nicolas, John Ball; Microglia suppression during hibernation prevents axonal injury-induced retinal ganglion cell death in the ground squirrel retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2512.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Hibernators, such as ground squirrels (GS), survive profound hypothermia without injury, a remarkable feat of cellular preservation with great medical potentials. We set out to examine whether they respond to neural tissue injury differently during hibernation.
Optic nerve crush (ONC) surgeries were performed in awake and hibernating GSs. Immunocytochemistry and confocal-imaging, multi-electrode array (MEA) recording, RNAseq, cytokine panel assay, and biochemical enzymatic activity measurements were employed to probe retinal ganglion cell (RGC) survival and function (up to three weeks post-surgery) as well as cellular responses at the injury site and in the retina.
Here we report that ONC, which results in ~80% retinal ganglion cell (RGC) death in awake GS, failed to cause RGC death in hibernating animals. This extraordinary neuronal survival appears to be associated with a lack of both microglia aggregation at the lesion site and activation in the retina. Through RNAseq comparison of the differential responses to ONC in awake and hibernating GSs, biochemical measurements of some key metabolic enzyme activities, and profiling of cytokine responses, we identified certain metabolic adaptations in the hibernating GSs that may impact the local immune response to injury. We therefore pharmacologically mimicked the metabolic regulation observed in hibernating GSs. Remarkably, microglia activation was suppressed and RGCs were preserved after ONC in awake GSs. Furthermore, depleting microglia in awake GSs also prevented axonal injury-induced RGC death.
Thus, using the hibernating GS as a model, we identified an important metabolic regulatory mechanism that inhibits microglia and deters neuronal death after axonal injury.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Upper panel: RGC density plots 14 days after ONC in awake GSs. Lower panel: RGC density plots 14 days after ONC in hibernating GSs.
This PDF is available to Subscribers Only