title: Aged complement factor H knockout mice kept in a clean barriered environment have reduced retinal pathology.
abstract: Age-related macular degeneration (AMD) is the largest cause of visual loss in those over 60 years in the West and is a condition increasing in prevalence. Many diseases result from genetic/environmental interactions and 50% of AMD cases have an association with polymorphisms of the complement system including complement factor H. Here we explore interactions between genetic predisposition and environmental conditions in triggering retinal pathology in two groups of aged complement factor H knock out (Cfh(-/-)) mice. Mice were maintained over 9 months in either a conventional open environment or a barriered pathogen free environment. Open environment Cfh(-/-) mice had significant increases in subretinal macrophage numbers, inflammatory and stress responses and reduced photoreceptor numbers over mice kept in a pathogen free environment. Hence, environmental factors can drive retinal disease in these mice when linked to complement deficits impairing immune function. Both groups of mice had similar levels of retinal amyloid beta accumulation. Consequently there is no direct link between this and inflammation in Cfh(-/-) mice.
authors.affiliation: Institute of Ophthalmology, University College London, UK.
authors.forename: Jaimie
authors.initials: J
authors.lastname: Hoh Kam
authors.affiliation: School of Optometry and Visual Science, Cardiff University, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Morgan
authors.affiliation: Institute of Ophthalmology, University College London, UK. Electronic address: g.jeffery@ucl.ac.uk.
authors.forename: Glen
authors.initials: G
authors.lastname: Jeffery
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D012160:Retina / Q000378:metabolism / Q000473:pathology*
chemical_list: D017242:Complement Factor H
keywords: Age-related macular degeneration; Factor H; Inflammation; Pathogens