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

Sean McCracken, Michael J. Fitzpatrick, Allison L. Hall, Zelun Wang, Daniel Kerschensteiner, Josh L. Morgan, Philip R. Williams

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number113165
JournalCell Reports
Volume42
Issue number10
DOIs
StatePublished - Oct 31 2023

Keywords

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

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