title: Characterisation of amyloid-induced inflammatory responses in the rat retina.
abstract: Amyloid-induced inflammation is thought to play a critical and early role in the pathophysiology of Alzheimer's disease. As such, robust models with relevant and accessible compartments that provide a means of assessing anti-inflammatory agents are essential for the development of therapeutic agents. In the present work, we have characterised the induction of inflammation in the rat retina following intravitreal administration of amyloid-beta protein (Aβ). Histology and mRNA endpoints in the retina demonstrate Aβ1-42-, but not Aβ42-1-, induced inflammatory responses characterised by increases in markers for microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1), GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines such as IL1-β, MIP1α and TNFα. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-β, MIP1α and MCP1, induced by Aβ1-42 but not Aβ42-1. This profile of pro-inflammatory gene and protein expression is consistent with that observed in the Alzheimer's disease brain and suggest that this preclinical model may provide a useful relevant tool in the development of anti-inflammatory approaches directed towards Alzheimer's disease therapy.
authors.affiliation: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. david.howlett@kcl.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Howlett
authors.forename: S T
authors.initials: ST
authors.lastname: Bate
authors.forename: S
authors.initials: S
authors.lastname: Collier
authors.forename: A
authors.initials: A
authors.lastname: Lawman
authors.forename: T
authors.initials: T
authors.lastname: Chapman
authors.forename: T
authors.initials: T
authors.lastname: Ashmeade
authors.forename: I
authors.initials: I
authors.lastname: Marshall
authors.forename: P J B
authors.initials: PJ
authors.lastname: Anderson
authors.forename: K L
authors.initials: KL
authors.lastname: Philpott
authors.forename: J C
authors.initials: JC
authors.lastname: Richardson
authors.forename: C J
authors.initials: CJ
authors.lastname: Hille
mesh_terms: D000682:Amyloid / Q000008:administration & dosage / Q000633:toxicity; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D058449:Intravitreal Injections; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012173:Retinitis / Q000209:etiology* / Q000473:pathology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)