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Experimental Brain Research

, 214:185 | Cite as

Characterisation of amyloid-induced inflammatory responses in the rat retina

  • D. R. HowlettEmail author
  • S. T. Bate
  • S. Collier
  • A. Lawman
  • T. Chapman
  • T. Ashmeade
  • I. Marshall
  • P. J. B. Anderson
  • K. L. Philpott
  • J. C. Richardson
  • C. J. Hille
Research Article

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.

Keywords

Amyloid Alzheimer’s disease Inflammation Retina Cytokine 

Notes

Conflict of interest

All authors, with the exception of PJBA, were employees of GlaxoSmithKline R&D at the time this work was undertaken.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • D. R. Howlett
    • 1
    • 4
    Email author
  • S. T. Bate
    • 2
  • S. Collier
    • 1
  • A. Lawman
    • 1
  • T. Chapman
    • 1
  • T. Ashmeade
    • 1
  • I. Marshall
    • 1
  • P. J. B. Anderson
    • 3
  • K. L. Philpott
    • 1
  • J. C. Richardson
    • 1
  • C. J. Hille
    • 1
  1. 1.Neurosciences Centre of Excellence for Drug DiscoveryGlaxoSmithKline R&D LimitedHarlow, EssexUK
  2. 2.Statistical SciencesGlaxoSmithKline R&D LimitedHarlow, EssexUK
  3. 3.Department of Cellular and Molecular NeuroscienceDivision of Neuroscience and Mental Health, Imperial College LondonLondonUK
  4. 4.Wolfson Centre for Age-Related DiseasesKing’s College LondonLondonUK

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