Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo
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+ elevation...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723011774 |
| _version_ | 1797674163340574720 |
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| author | Sean McCracken Michael J. Fitzpatrick Allison L. Hall Zelun Wang Daniel Kerschensteiner Josh L. Morgan Philip R. Williams |
| author_facet | Sean McCracken Michael J. Fitzpatrick Allison L. Hall Zelun Wang Daniel Kerschensteiner Josh L. Morgan Philip R. Williams |
| author_sort | Sean McCracken |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T21:55:05Z |
| format | Article |
| id | doaj.art-c709596da627414f8eb562e591c80e11 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T21:55:05Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c709596da627414f8eb562e591c80e112023-09-26T04:12:07ZengElsevierCell Reports2211-12472023-10-014210113165Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivoSean McCracken0Michael J. Fitzpatrick1Allison L. Hall2Zelun Wang3Daniel Kerschensteiner4Josh L. Morgan5Philip R. Williams6John 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, USAJohn 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, USAJohn 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, USAJohn 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, USAJohn 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, USAJohn 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, USAJohn 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723011774CP: Neuroscience |
| spellingShingle | Sean McCracken Michael J. Fitzpatrick Allison L. Hall Zelun Wang Daniel Kerschensteiner Josh L. Morgan Philip R. Williams Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo Cell Reports CP: Neuroscience |
| title | Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| title_full | Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| title_fullStr | Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| title_full_unstemmed | Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| title_short | Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| title_sort | diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723011774 |
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