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EMBO Mol Med. 2016 Dec 1;8(12):1366-1379. doi: 10.15252/emmm.201606531. Print 2016 Dec.

Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.

Author information

1
Department of Biomedical Sciences, Maisonneuve-Rosemont Hospital Research Centre University of Montreal, Montreal, Quebec, Canada.
2
Department of Engineering Physics, Laser Processing and Plasmonics Laboratory École Polytechnique de Montréal, Montreal, Quebec, Canada.
3
Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
4
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
5
Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec, Canada.
6
INSERM, U 968, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche S 968, Institut de la Vision, CNRS, Unité Mixte de Recherche, Paris, France.
7
Department of Biomedical Sciences, Maisonneuve-Rosemont Hospital Research Centre University of Montreal, Montreal, Quebec, Canada mike.sapieha@umontreal.ca.

Abstract

Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late-stage NV AMD To date, the mechanisms that underscore this observation remain ill-defined. Given the impact of high-fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high-fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low-grade inflammation characteristic of inflammaging with elevated production of IL-6, IL-1β, TNF-α, and VEGF-A that ultimately aggravate pathological angiogenesis.

KEYWORDS:

age‐related macular degeneration; angiogenesis; gut microbiota; inflammaging; obesity

PMID:
27861126
PMCID:
PMC5167134
DOI:
10.15252/emmm.201606531
[Indexed for MEDLINE]
Free PMC Article

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