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Updated: Jun 6, 2025

Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP
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Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP

Published on: September 6, 2015

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Endoplasmic reticulum stress-related deficits in calcium clearance promote neuronal dysfunction that is prevented by

Yukihiro Shiga1, Aline Giselle Rangel Olguin2, Sana El Hajji1

  • 1Department of Neuroscience, University of Montreal, PO box 6128, Station Centre-ville, Montreal, Quebec H3C 3J7, Canada; Neuroscience Division, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 Saint Denis Street, Montreal, Quebec H2X 0A9, Canada.

Cell Reports. Medicine
|November 30, 2024
PubMed

Insights

Restoring calcium (Ca2+) regulation in retinal neurons by enhancing SERCA2 pump function can reverse vision loss and neurodegeneration. This approach alleviates endoplasmic reticulum stress and restores neural circuit balance for improved visual behaviors.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Ophthalmology

Background:

  • Disruption of calcium (Ca2+) homeostasis is a key feature of neurodegenerative diseases, impacting neuronal function.
  • Ocular hypertension and optic nerve injury are risk factors for glaucoma, leading to retinal neuron damage.
  • Altered Ca2+ dynamics can contribute to neuronal stress and circuit dysfunction.

Purpose of the Study:

  • To investigate the mechanisms of Ca2+ dysregulation in retinal neurons following injury.
  • To determine if impaired Ca2+ dynamics affect neuronal stress and circuit function.
  • To explore therapeutic strategies for restoring Ca2+ homeostasis and promoting neuroprotection in glaucoma.

Main Methods:

  • Two-photon microscopy to assess Ca2+ dynamics in retinal neurons.
  • Gene and protein expression analysis to identify molecular changes in injured neurons.
  • Pharmacological and gene therapy approaches to modulate SERCA2 pump activity.

Main Results:

  • Ocular hypertension and optic nerve crush injury impair cytosolic Ca2+ clearance in retinal neurons, affecting light responses.
  • Loss of the sarco-endoplasmic reticulum Ca2+-ATPase2 (SERCA2) pump was observed in injured retinal neurons from mice and glaucoma patients.
  • SERCA2 activation or gene delivery rescued Ca2+ dynamics, enhanced neuronal survival, reduced ER stress, and restored visual behaviors.

Conclusions:

  • Enhancing Ca2+ clearance capacity through SERCA2 restoration is a viable therapeutic strategy for neurodegenerative conditions like glaucoma.
  • Targeting SERCA2 can alleviate endoplasmic reticulum stress and promote neurorecovery in damaged neurons.
  • Restoring Ca2+ homeostasis is crucial for maintaining neuronal function and circuit balance, leading to improved visual outcomes.
Keywords:
calcium homeostasisendoplasmic reticulum stressgene therapyglaucomain vivo imagingneurodegenerationorganelle stressretinal ganglion cellsarco-endoplasmic reticulum (ER) calcium-ATPase2 pump (SERCA2/ATP2A2)traumatic optic neuropathy

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