Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo

Abstract

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca²⁺ levels to RGC death from axon injury. We find that axonal Ca²⁺ elevations from optic nerve injury do not propagate over distance or reach RGC somas, and acute and chronic Ca²⁺ dynamics do not affect RGC survival. Instead, we discover that baseline Ca²⁺ levels vary widely between RGCs and predict their survival after axon injury, and that lowering these levels reduces RGC survival. Further, we find that well-surviving RGC types have higher baseline Ca²⁺ levels than poorly surviving types. Finally, we observe considerable variation in the baseline Ca²⁺ levels of different RGCs of the same type, which are predictive of within-type differences in survival.

Keywords: CP: Neuroscience; calcium homeostasis; in vivo imaging; neuronal degeneration; optic nerve crush; retinal ganglion cells.