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: D R Howlett, 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
• Journal: Experimental brain research (Exp Brain Res) Vol. 214 Issue 2 Pg. 185-97 (Oct 2011) ISSN: 1432-1106 [Electronic] Germany
• PMID: 21850448 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• Biomarkers
• Chemokines
• Cytokines
• Peptide Fragments
• amyloid beta-protein (1-42)

Topics

• Amyloid (administration & dosage, toxicity)
• Amyloid beta-Peptides (administration & dosage, toxicity)
• Animals
• Astrocytes (metabolism, pathology)
• Biomarkers (metabolism)
• Chemokines (biosynthesis)
• Cytokines (biosynthesis)
• Female
• Humans
• Inflammation (etiology, metabolism, pathology)
• Intravitreal Injections
• Microglia (metabolism, pathology)
• Peptide Fragments (administration & dosage, toxicity)
• Rats
• Retina (metabolism, pathology)
• Retinitis (etiology, pathology)