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
Affiliations
Sean McCracken
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA
Michael J. Fitzpatrick
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA
Allison L. Hall
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Postbaccalaureate Program in Developmental Biology & Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Zelun Wang
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA
Daniel Kerschensteiner
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63110, USA
Josh L. Morgan
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA
Philip R. Williams
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: 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.
