caa a22 4500 445350776 CHVBK 20180317142843.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00221-011-2819-4 doi (NATIONALLICENCE)springer-10.1007/s00221-011-2819-4 Characterisation of amyloid-induced inflammatory responses in the rat retina [Elektronische Daten] [D. Howlett, S. Bate, S. Collier, A. Lawman, T. Chapman, T. Ashmeade, I. Marshall, P. Anderson, K. Philpott, J. Richardson, C. Hille] 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. Springer-Verlag, 2011 Amyloid nationallicence Alzheimer's disease nationallicence Inflammation nationallicence Retina nationallicence Cytokine nationallicence Howlett D. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Bate S. Statistical Sciences, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Collier S. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Lawman A. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Chapman T. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Ashmeade T. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Marshall I. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Anderson P. Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, W6 8RF, London, UK aut Philpott K. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Richardson J. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Hille C. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut Experimental Brain Research Springer-Verlag 214/2(2011-10-01), 185-197 0014-4819 214:2<185 2011 214 221 https://doi.org/10.1007/s00221-011-2819-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00221-011-2819-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Howlett D. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Bate S. Statistical Sciences, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Collier S. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Lawman A. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Chapman T. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Ashmeade T. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Marshall I. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Anderson P. Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, W6 8RF, London, UK aut NATIONALLICENCE 700 1- Philpott K. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Richardson J. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Hille C. Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK aut NATIONALLICENCE 773 0- Experimental Brain Research Springer-Verlag 214/2(2011-10-01), 185-197 0014-4819 214:2<185 2011 214 221 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer