Characterisation of amyloid-induced inflammatory responses in the rat retina
- 422 Downloads
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.
KeywordsAmyloid Alzheimer’s disease Inflammation Retina Cytokine
Conflict of interest
All authors, with the exception of PJBA, were employees of GlaxoSmithKline R&D at the time this work was undertaken.
- Bosco P, Guéant-Rodríguez RM, Anello G, Romano A, Namour B, Spada RS, Caraci F, Tringali G, Ferri R, Guéant JL (2004) Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:1036–1038PubMedCrossRefGoogle Scholar
- Hampel H, Haslinger A, Scheloske M, Padberg F, Fischer P, Unger J, Teipel SJ, Neumann M, Rosenberg C, Oshida R, Hulette C, Pongratz D, Ewers M, Kretzschmar HA, Möller HJ (2005) Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer’s disease brain. Eur Arch Psychiatry Clin Neurosci 255:269–278PubMedCrossRefGoogle Scholar
- Howlett DR, Bowler K, Soden PE, Riddell D, Davis JB, Richardson JC, Burbidge SA, Gonzalez MI, Irving EA, Lawman A, Miglio G, Dawson EL, Howlett ER, Hussain I (2008) Abeta deposition and related pathology in an APP × PS1 transgenic mouse model of Alzheimer’s disease. Histol Histopathol 23:67–76PubMedGoogle Scholar
- Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovici GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirani R, Wyss-Coray T (2007) Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 13:1359–1362PubMedCrossRefGoogle Scholar