title: Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration.
abstract: Extra-cellular deposition including amyloid beta (Aβ) is a feature of retinal ageing. It has been documented for Bruch's membrane (BM) where Aβ is elevated in complement factor H knockout mice (Cfh(-/-)) proposed as a model for age related macular degeneration. However, arterial deposition in choroidal vessels prior to perfusion across BM has not been examined. Aβ is associated with tau phosphorylation and these are linked in blood vessels in Alzheimers Disease where they can drive perivascular pathology. Here we ask if Aβ, tau and phosphorylated tau are features of ageing in choroidal vessels in 12 month C57 BL/6 and Cfh(-/-) mice, using immune staining and Western blot analysis. Greater levels of Aβ and phosphorylated tau are found in choroidal vessels in Cfh(-/-) mice. Western blot revealed a 40% increase in Aβ in Cfh(-/-) over C57 BL/6 mice. Aβ deposits coat around 55% of the luminal wall in Cfh(-/-) compared to only about 40% in C57 BL/6. Total tau was similar in both groups, but phosphorylated tau increased by >100% in Cfh(-/-) compared to C57 BL/6 and covered >75% of the luminal wall compared to 50% in C57 BL/6. Hence, phosphorylated tau is a marked choroidal feature in this mouse model. Aβ deposition was clumped in Cfh(-/-) mice and likely to influence blood flow dynamics. Disturbed flow is associated with atherogenesis and may be related to the accumulation of membrane attack complex recently identified between choroidal vessels in those at high risk of macular degeneration due to complement factor H polymorphisms.
authors.affiliation: Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Egypt.
authors.forename: Asmaa
authors.initials: A
authors.lastname: Aboelnour
authors.affiliation: Institute of Ophthalmology, University College London, UK.
authors.forename: Jaimie Hoh
authors.initials: JH
authors.lastname: Kam
authors.affiliation: Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Egypt.
authors.forename: M A
authors.initials: MA
authors.lastname: Elnasharty
authors.affiliation: Anatomy Department, Faculty of Veterinary Medicine, Damanhour University, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sayed-Ahmed
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: D000375:Aging / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D015153:Blotting, Western; D002829:Choroid / Q000378:metabolism*; D017242:Complement Factor H / Q000172:deficiency*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012162:Retinal Degeneration / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D017242:Complement Factor H
keywords: Aging; Amyloid beta; Macular degeneration; Retina; Tau