Characterisation of amyloid-induced inflammatory responses in the rat retina

Characterisation of amyloid-induced inflammatory responses in the rat retina
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DOI:
10.1007/s00221-011-2819-4
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发表时间:
2011-10-01
影响因子:
2
通讯作者:
Hille, C. J.
Hille, C. J.
中科院分区:
医学4区
文献类型:
--
作者:
Howlett, D. R.;Bate, S. T.;Hille, C. J.

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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 (A beta). Histology and mRNA endpoints in the retina demonstrate A beta 1-42-, but not A beta 42-1-, 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-beta, MIP1 alpha and TNF alpha. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-beta, MIP1 alpha and MCP1, induced by A beta 1-42 but not A beta 42-1. This profile of proinflammatory 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.