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The mito -QC Reporter for Quantitative Mitophagy Assessment in Primary Retinal Ganglion Cells and Experimental Glaucoma Models

Authors
  • Rosignol, Ines1
  • Villarejo-Zori, Beatriz1
  • Teresak, Petra1
  • Sierra-Filardi, Elena1
  • Pereiro, Xandra2
  • Rodríguez-Muela, Natalia1
  • Vecino, Elena2
  • Vieira, Helena L. A.3, 4
  • Bell, Katharina1
  • Boya, Patricia1
  • 1 Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040 Madrid, Spain
  • 2 Experimental-Ophthalmo-Biology Group, Universidad del País Vasco, 48950 Leioa, Spain
  • 3 UCIBIO, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal
  • 4 CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1150-082 Lisbon, Portugal
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Mar 10, 2020
Volume
21
Issue
5
Identifiers
DOI: 10.3390/ijms21051882
PMID: 32164182
PMCID: PMC7084520
Source
PubMed Central
Keywords
License
Green

Abstract

Mitochondrial damage plays a prominent role in glaucoma. The only way cells can degrade whole mitochondria is via autophagy, in a process called mitophagy. Thus, studying mitophagy in the context of glaucoma is essential to understand the disease. Up to date limited tools are available for analyzing mitophagy in vivo. We have taken advantage of the mito -QC reporter, a recently generated mouse model that allows an accurate mitophagy assessment to fill this gap. We used primary RGCs and retinal explants derived from mito -QC mice to quantify mitophagy activation in vitro and ex vivo. We also analyzed mitophagy in retinal ganglion cells (RGCs), in vivo, using different mitophagy inducers, as well as after optic nerve crush (ONC) in mice, a commonly used surgical procedure to model glaucoma. Using mito -QC reporter we quantified mitophagy induced by several known inducers in primary RGCs in vitro, ex vivo and in vivo. We also found that RGCs were rescued from some glaucoma relevant stress factors by incubation with the iron chelator deferiprone (DFP). Thus, the mito -QC reporter-based model is a valuable tool for accurately analyzing mitophagy in the context of glaucoma.

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