An SPM-Enriched Marine Oil Supplement Shifted Microglia Polarization toward M2, Ameliorating Retinal Degeneration in rd10 Mice.
Por:
Olivares-González L, Velasco S, Gallego I, Esteban-Medina M, Puras G, Loucera C, Martínez-Romero A, Peña-Chilet M, Pedraz JL and Rodrigo R
Publicada:
30 dic 2022
Resumen:
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement.
Filiaciones:
:
Group of Pathophysiology and Therapies for Vision Disorders, Príncipe Felipe Research Center (CIPF), 46012 Valencia, Spain
:
Group of Pathophysiology and Therapies for Vision Disorders, Príncipe Felipe Research Center (CIPF), 46012 Valencia, Spain
Gallego I:
NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Health Institute Carlos III, 01006 Vitoria-Gasteiz, Spain
Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
Esteban-Medina M:
Computational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS Hospital Virgen del Rocío, 41013 Seville, Spain
Systems and Computational Medicine Group, Institute of Biomedicine of Seville, IBiS, University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain
Puras G:
NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Health Institute Carlos III, 01006 Vitoria-Gasteiz, Spain
Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
Loucera C:
Computational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS Hospital Virgen del Rocío, 41013 Seville, Spain
Systems and Computational Medicine Group, Institute of Biomedicine of Seville, IBiS, University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain
:
Cytomic Unit, Príncipe Felipe Research Center (CIPF), 46012 Valencia, Spain
Peña-Chilet M:
Computational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS Hospital Virgen del Rocío, 41013 Seville, Spain
Systems and Computational Medicine Group, Institute of Biomedicine of Seville, IBiS, University Hospital Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain
Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), FPS, Hospital Virgen del Rocio, 41013 Seville, Spain
Pedraz JL:
NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Health Institute Carlos III, 01006 Vitoria-Gasteiz, Spain
Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
:
Group of Pathophysiology and Therapies for Vision Disorders, Príncipe Felipe Research Center (CIPF), 46012 Valencia, Spain
Biomedical Research Networking Center in Rare Diseases (CIBERER), Health Institute Carlos III, 28029 Madrid, Spain
Department of Physiology, University of Valencia (UV), 46100 Burjassot, Spain
Department of Anatomy and Physiology, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics UV-IIS La Fe, 46026 Valencia, Spain
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