title: Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.
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.
authors.affiliation: Department of Biomedical Sciences, Maisonneuve-Rosemont Hospital Research Centre University of Montreal, Montreal, Quebec, Canada.
authors.forename: Elisabeth Mma
authors.initials: EM
authors.lastname: Andriessen
authors.affiliation: Department of Engineering Physics, Laser Processing and Plasmonics Laboratory École Polytechnique de Montréal, Montreal, Quebec, Canada.
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Wilson
authors.affiliation: Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Mawambo
authors.affiliation: Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.|Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dejda
authors.affiliation: Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Miloudi
authors.affiliation: 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.
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.affiliation: Department of Biomedical Sciences, Maisonneuve-Rosemont Hospital Research Centre University of Montreal, Montreal, Quebec, Canada mike.sapieha@umontreal.ca.|Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.|Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.|Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Przemyslaw
authors.identifier: 0000-0002-9171-2825
authors.initials: P
authors.lastname: Sapieha
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000209:etiology; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007249:Inflammation / Q000473:pathology; D008268:Macular Degeneration / Q000453:epidemiology / Q000473:pathology*; D051379:Mice; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000150:complications* / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: age‐related macular degeneration; angiogenesis; gut microbiota; inflammaging; obesity