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The Role of Amyloid-β in Retinal Degeneration

  • Julien BrubanEmail author
  • Virginie Dinet
  • Frédéric Mascarelli
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in western countries. It is characterized by the formation of subretinal deposits called drusen, associated with atrophy of the retinal pigment epithelium (RPE), disturbance of the transepithelial barrier, and photoreceptor death. AMD is a complex disease involving many genetic and environmental factors that may confound one another. Although the mechanisms of AMD are not yet clearly understood, the observation of amyloid-β (Aβ), a protein commonly associated with Alzheimer’s disease (AD), within RPE cells and drusen in AMD patients is consistent with the hypothesis that the disease is mediated by oxidative stress and inflammatory processes. Several lines of evidence pinpoint the role of Aβ in RPE dysfunction, and retinal inflammation and alteration leading to retinal degeneration. This review summarizes current knowledge relating to the potential role of Aβ in retinal degeneration with emphasis on AMD.

Keywords

AMD Amyloïd-β Retina Inflammation Degeneration Drusen RPE Cytotoxicity Complement 

References

  1. Anderson DH, Talaga KC, Rivest AJ et al (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 78:243–256PubMedCrossRefGoogle Scholar
  2. Anderson PJ, Watts H, Hille C et al (2008) Glial and endothelial blood-retinal barrier responses to amyloid-beta in the neural retina of the rat. Clin Ophthalmol. 2:801–816PubMedCrossRefGoogle Scholar
  3. Blanks JC, Torigoe Y, Hinton DR et al (1991). Retinal degeneration in the macula of patients with Alzheimer’s disease. Ann N Y Acad Sci. 640:44–46PubMedGoogle Scholar
  4. Bruban J, Glotin AL, Dinet V et al (2009) Amyloid-beta(1–42) alters structure and function of retinal pigmented epithelial cells. Aging Cell. 8:162–177PubMedCrossRefGoogle Scholar
  5. Bruban J, Maoui A, Chalour N et al (2011) CCR2/CCL2-mediated inflammation protects photo­receptor cells from amyloid-β-induced apoptosis. Neurobiol Dis. 42:55–72Google Scholar
  6. Coffey PJ, Gias C, McDermott et al (2007) Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction. Proc Natl Acad Sci U S A. 104:16651–16656PubMedCrossRefGoogle Scholar
  7. Coleman HR, Chan CC, Ferris FL et al (2008) Age-related macular degeneration. Lancet. 372:1835–1845PubMedCrossRefGoogle Scholar
  8. Crabb JW, Miyagi M, Gu X et al (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A. 99:14682–14687PubMedCrossRefGoogle Scholar
  9. Dentchev T, Milam AH, Lee VM et al (2003) Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis 9:184–190PubMedGoogle Scholar
  10. Ding JD, Lin J, Mace BE et al (2008) Targeting age-related macular degeneration with Alzheimer’s disease based immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an age-related macular degeneration mouse model. Vision Res. 48:339–345PubMedCrossRefGoogle Scholar
  11. Ding X, Patel M and Chan CC (2009) Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 28:1–18PubMedCrossRefGoogle Scholar
  12. Dunaief JL, Dentchev T, Ying GS et al (2002) The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 120:1435–1442PubMedGoogle Scholar
  13. Edwards AO, Ritter R 3 rd Abel KJ et al (2005) Complement factor H polymorphism and age-related macular degeneration. Science. 308:421–424PubMedCrossRefGoogle Scholar
  14. Green WR (1999) Histopathology of age-related macular degeneration. Mol Vis. 5:27PubMedGoogle Scholar
  15. Glabe CG an Kayed R (2006) Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis. Neurology. 66:S74-78PubMedCrossRefGoogle Scholar
  16. Glotin AL, Debacq-Chainiaux F, Brossas Y et al (2008) Prematurely senescent ARPE-19 cells display features of age-related macular degeneration. Free Radic Biol Med. 44:1348–1361PubMedCrossRefGoogle Scholar
  17. Gold B, Merriam JE, Zernant J et al (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet. 38:458–462PubMedCrossRefGoogle Scholar
  18. Goldblum D, Kipfer-Kauer A, Sarra GM et al (2007) Distribution of amyloid precursor protein and amyloid-beta immunoreactivity in DBA/2 J glaucomatous mouse retinas. Invest Ophthalmol Vis Sci. 48:5085–5090PubMedCrossRefGoogle Scholar
  19. Guo L, Salt TE, Luong V et al (2007) Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci U S A. 104:13444–13449PubMedCrossRefGoogle Scholar
  20. Hageman GS, Anderson DH, Johnson LV et al (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A 102:7227–7232PubMedCrossRefGoogle Scholar
  21. Haines JL, Hauser MA, Schmidt S et al (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science. 308:419–421PubMedCrossRefGoogle Scholar
  22. Isas JM, Luibl V, Johnson LV et al (2010) Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci. 51:1304–1310PubMedCrossRefGoogle Scholar
  23. Iwata N, Tsubuki S, Takaki Y et al (2000) Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med. 6:143–150PubMedCrossRefGoogle Scholar
  24. Johnson LV, Leitner WP, Rivest AJ et al (2002) The Alzheimer’s Abeta peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A. 99:11830–11835PubMedCrossRefGoogle Scholar
  25. Johnson LV, Leitner WP, Staples MK et al (2001) Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res. 73:887–896PubMedCrossRefGoogle Scholar
  26. Johnson LV, Ozaki S, Staples MK et al (2000) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res. 70:441–449PubMedCrossRefGoogle Scholar
  27. Johnson PT, Lewis GP, Talaga KC et al (2003) Drusen-associated degeneration in the retina. Invest Ophthalmol Vis Sci. 44:4481–4488PubMedCrossRefGoogle Scholar
  28. Klein R, Peto T, Bird A et al (2004) The epidemiology of age-related macular degeneration Am J Ophthalmol. 137:486–495Google Scholar
  29. Klein RJ, Zeiss C, Chew EY et al (2005) Complement factor H polymorphism in age-related macular degeneration. Science. 308:385–389PubMedCrossRefGoogle Scholar
  30. Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV et al (2010) Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. NeuroimageGoogle Scholar
  31. Koyama Y, Matsuzaki S, Gomi F et al (2008) Induction of amyloid beta accumulation by ER calcium disruption and resultant upregulation of angiogenic factors in ARPE19 cells. Invest Ophthalmol Vis Sci. 49:2376–2383PubMedCrossRefGoogle Scholar
  32. Kurji KH, Cui JZ, Lin T et al (2010) Microarray analysis identifies changes in inflammatory gene expression in response to amyloid-beta stimulation of cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 51:1151–1163PubMedCrossRefGoogle Scholar
  33. Lambert MP, Barlow AK, Chromy BA et al (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A. 95:6448–6453PubMedCrossRefGoogle Scholar
  34. Liu B, Rasool S, Yang Z et al (2009) Amyloid-peptide vaccinations reduce {beta}-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer’s transgenic mice. Am J Pathol. 175:2099–2110PubMedCrossRefGoogle Scholar
  35. Luibl V, Isas JM, Kayed R et al (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest. 116:378–385PubMedCrossRefGoogle Scholar
  36. Mullins RF, Russell SR, Anderson, DH et al (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. Faseb J 14:835–846PubMedGoogle Scholar
  37. Ning A, Cui J, To E et al (2008). Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest Ophthalmol Vis Sci. 49:5136–5143PubMedCrossRefGoogle Scholar
  38. Perez SE, Lumayag S, Kovacs B et al (2009) Beta-amyloid deposition and functional impairment in the retina of the APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer’s disease. Invest Ophthalmol Vis Sci. 50:793–800PubMedCrossRefGoogle Scholar
  39. Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 81:741–766PubMedGoogle Scholar
  40. Seth A, Cui J, To E, et al (2008) Complement-associated deposits in the human retina. Invest Ophthalmol Vis Sci. 49:743–750PubMedCrossRefGoogle Scholar
  41. Tsuruma K, Tanaka Y, Shimazawa M et al (2010) Induction of amyloid precursor protein by the neurotoxic peptide, amyloid-beta 25–35, causes retinal ganglion cell death. Neurochem. 113:1545–1554Google Scholar
  42. Walsh DT, Bresciani L, Saunders D et al (2005) Amyloid beta peptide causes chronic glial cell activation and neuro-degeneration after intravitreal injection. Neuropathol Appl Neurobiol. 31:491–502PubMedCrossRefGoogle Scholar
  43. Walsh DT, Montero RM, Bresciani LG et al (2002) Amyloïd-beta peptide is toxic to neurons in vivo via indirect mechanisms. Neurobiol Dis. 10:20–27PubMedCrossRefGoogle Scholar
  44. Wang J, Ohno-Matsui K, Yoshida T et al (2009) Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia. J Cell Physiol. 220:119–128PubMedCrossRefGoogle Scholar
  45. Wang, J, Ohno-Matsui K., Yoshida T et al (2008) Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen. J Immunol. 181:712–720.PubMedGoogle Scholar
  46. Yates JR, Sepp T, Matharu BK et al (2007) Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 357:553–561PubMedCrossRefGoogle Scholar
  47. Yoshida T, Ohno-Matsui K, Ichinose, S et al (2005) The potential role of amyloid beta in the pathogenesis of age-related macular degeneration. J Clin Invest 115:2793–2800PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Julien Bruban
    • 1
    • 2
    • 3
    Email author
  • Virginie Dinet
    • 1
    • 2
    • 3
  • Frédéric Mascarelli
    • 1
    • 2
    • 3
  1. 1.Centre de Recherche des CordeliersUniversité Pierre et Marie Curie – Paris 6ParisFrance
  2. 2.Université Paris Descartes, UMRS 872ParisFrance
  3. 3.INSERM, UMRS872ParisFrance

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