Characterisation of Amyloid-induced Inflammatory Responses in the Rat Retina

Overview

Journal Exp Brain Res

Specialty Neurology

Date 2011 Aug 19

PMID 21850448

Citations 13

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

Affiliations

Soon will be listed here.

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.

Citing Articles

The Past and Present Lives of the Intraocular Transmembrane Protein CD36.

Yang R, Liu Q, Zhang M Cells. 2023; 12(1).

PMID: 36611964 PMC: 9818597. DOI: 10.3390/cells12010171.

Epigenetics in age-related macular degeneration: new discoveries and future perspectives.

Gemenetzi M, Lotery A Cell Mol Life Sci. 2020; 77(5):807-818.

PMID: 31897542 PMC: 7058675. DOI: 10.1007/s00018-019-03421-w.

Dantrolene : From Malignant Hyperthermia to Alzheimer's Disease.

Shi Y, Wang Y, Wei H CNS Neurol Disord Drug Targets. 2018; 18(9):668-676.

PMID: 29921212 PMC: 7754833. DOI: 10.2174/1871527317666180619162649.

Cooperation of Rel family members in regulating Aβ-mediated pro-inflammatory cytokine secretion by retinal pigment epithelial cells.

Sun J, Huang P, Liang J, Li J, Shen M, She X Cell Death Dis. 2017; 8(10):e3115.

PMID: 29022897 PMC: 5682668. DOI: 10.1038/cddis.2017.502.

The complexities underlying age-related macular degeneration: could amyloid beta play an important role?.

Lynn S, Keeling E, Munday R, Gabha G, Griffiths H, Lotery A Neural Regen Res. 2017; 12(4):538-548.

PMID: 28553324 PMC: 5436342. DOI: 10.4103/1673-5374.205083.

References

Bustin S . Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000; 25(2):169-93. DOI: 10.1677/jme.0.0250169. View

Luth H, Munch G, Arendt T . Aberrant expression of NOS isoforms in Alzheimer's disease is structurally related to nitrotyrosine formation. Brain Res. 2002; 953(1-2):135-43. DOI: 10.1016/s0006-8993(02)03280-8. View

Meda L, Baron P, Prat E, Scarpini E, Scarlato G, Cassatella M . Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid[25-35]. J Neuroimmunol. 1999; 93(1-2):45-52. DOI: 10.1016/s0165-5728(98)00188-x. View

Anderson P, Watts H, Hille C, Philpott K, Clark P, Gentleman M . Glial and endothelial blood-retinal barrier responses to amyloid-beta in the neural retina of the rat. Clin Ophthalmol. 2009; 2(4):801-16. PMC: 2699783. DOI: 10.2147/opth.s3967. View

Vehmas A, Kawas C, Stewart W, Troncoso J . Immune reactive cells in senile plaques and cognitive decline in Alzheimer's disease. Neurobiol Aging. 2002; 24(2):321-31. DOI: 10.1016/s0197-4580(02)00090-8. View

Laws S, Perneczky R, Wagenpfeil S, Muller U, Forstl H, Martins R . TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum Mutat. 2005; 26(1):29-35. DOI: 10.1002/humu.20180. View

Lue L, Rydel R, Brigham E, Yang L, Hampel H, Murphy Jr G . Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro. Glia. 2001; 35(1):72-9. DOI: 10.1002/glia.1072. View

Galimberti D, Fenoglio C, Lovati C, Venturelli E, Guidi I, Corra B . Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease. Neurobiol Aging. 2005; 27(12):1763-8. DOI: 10.1016/j.neurobiolaging.2005.10.007. View

Floden A, Combs C . Beta-amyloid stimulates murine postnatal and adult microglia cultures in a unique manner. J Neurosci. 2006; 26(17):4644-8. PMC: 6674057. DOI: 10.1523/JNEUROSCI.4822-05.2006. View

10.

Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K . Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med. 2007; 13(11):1359-62. DOI: 10.1038/nm1653. View

11.

Zhu X, Rottkamp C, Boux H, Takeda A, Perry G, Smith M . Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J Neuropathol Exp Neurol. 2000; 59(10):880-8. DOI: 10.1093/jnen/59.10.880. View

12.

Cornelius C, Fastbom J, Winblad B, Viitanen M . Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology. 2004; 23(3):135-43. DOI: 10.1159/000075957. View

13.

Alvarez V, Mata I, Gonzalez P, Lahoz C, Martinez C, Pena J . Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease. Am J Med Genet. 2002; 114(5):574-7. DOI: 10.1002/ajmg.10515. View

14.

White J, Manelli A, Holmberg K, Van Eldik L, LaDu M . Differential effects of oligomeric and fibrillar amyloid-beta 1-42 on astrocyte-mediated inflammation. Neurobiol Dis. 2005; 18(3):459-65. DOI: 10.1016/j.nbd.2004.12.013. View

15.

Cacabelos R, Alvarez X, Fernandez-Novoa L, Franco A, Mangues R, Pellicer A . Brain interleukin-1 beta in Alzheimer's disease and vascular dementia. Methods Find Exp Clin Pharmacol. 1994; 16(2):141-51. View

16.

McGeer P, Rogers J . Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology. 1992; 42(2):447-9. DOI: 10.1212/wnl.42.2.447. View

17.

Lorton D, Schaller J, Lala A, De Nardin E . Chemotactic-like receptors and Abeta peptide induced responses in Alzheimer's disease. Neurobiol Aging. 2000; 21(3):463-73. DOI: 10.1016/s0197-4580(00)00092-0. View

18.

Liu B, Rasool S, Yang Z, Glabe C, Schreiber S, Ge J . Amyloid-peptide vaccinations reduce {beta}-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer's transgenic mice. Am J Pathol. 2009; 175(5):2099-110. PMC: 2774073. DOI: 10.2353/ajpath.2009.090159. View

19.

Frautschy S, Yang F, Irrizarry M, Hyman B, Saido T, Hsiao K . Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol. 1998; 152(1):307-17. PMC: 1858113. View

20.

Bosco P, Gueant-Rodriguez R, Anello G, Romano A, Namour B, Spada R . 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. 2004; 75(7):1036-8. PMC: 1739095. DOI: 10.1136/jnnp.2003.025866. View