Skip to main content
SpringerLink
Log in
SpringerLink
Log in

The Role of Amyloid-β in Retinal Degeneration

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 78:243–256

    Article  PubMed  CAS  Google Scholar 

  • 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. 2:801–816

    Article  PubMed  CAS  Google Scholar 

  • 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. 640:44–46

    PubMed  CAS  Google Scholar 

  • Bruban J, Glotin AL, Dinet V et al (2009) Amyloid-beta(1–42) alters structure and function of retinal pigmented epithelial cells. Aging Cell. 8:162–177

    Article  PubMed  CAS  Google Scholar 

  • Bruban J, Maoui A, Chalour N et al (2011) CCR2/CCL2-mediated inflammation protects photo­receptor cells from amyloid-β-induced apoptosis. Neurobiol Dis. 42:55–72

    Google Scholar 

  • 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. 104:16651–16656

    Article  PubMed  CAS  Google Scholar 

  • Coleman HR, Chan CC, Ferris FL et al (2008) Age-related macular degeneration. Lancet. 372:1835–1845

    Article  PubMed  CAS  Google Scholar 

  • 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. 99:14682–14687

    Article  PubMed  CAS  Google Scholar 

  • 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 9:184–190

    PubMed  CAS  Google Scholar 

  • 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. 48:339–345

    Article  PubMed  CAS  Google Scholar 

  • Ding X, Patel M and Chan CC (2009) Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 28:1–18

    Article  PubMed  CAS  Google Scholar 

  • Dunaief JL, Dentchev T, Ying GS et al (2002) The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 120:1435–1442

    PubMed  Google Scholar 

  • Edwards AO, Ritter R 3 rd Abel KJ et al (2005) Complement factor H polymorphism and age-related macular degeneration. Science. 308:421–424

    Article  PubMed  CAS  Google Scholar 

  • Green WR (1999) Histopathology of age-related macular degeneration. Mol Vis. 5:27

    PubMed  CAS  Google Scholar 

  • Glabe CG an Kayed R (2006) Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis. Neurology. 66:S74-78

    Article  PubMed  CAS  Google Scholar 

  • 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. 44:1348–1361

    Article  PubMed  CAS  Google Scholar 

  • 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. 38:458–462

    Article  PubMed  CAS  Google Scholar 

  • 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. 48:5085–5090

    Article  PubMed  Google Scholar 

  • Guo L, Salt TE, Luong V et al (2007) Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci U S A. 104:13444–13449

    Article  PubMed  CAS  Google Scholar 

  • 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 102:7227–7232

    Article  PubMed  CAS  Google Scholar 

  • Haines JL, Hauser MA, Schmidt S et al (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science. 308:419–421

    Article  PubMed  CAS  Google Scholar 

  • Isas JM, Luibl V, Johnson LV et al (2010) Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci. 51:1304–1310

    Article  PubMed  Google Scholar 

  • 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. 6:143–150

    Article  PubMed  CAS  Google Scholar 

  • 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. 99:11830–11835

    Article  PubMed  CAS  Google Scholar 

  • 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. 73:887–896

    Article  PubMed  CAS  Google Scholar 

  • Johnson LV, Ozaki S, Staples MK et al (2000) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res. 70:441–449

    Article  PubMed  CAS  Google Scholar 

  • Johnson PT, Lewis GP, Talaga KC et al (2003) Drusen-associated degeneration in the retina. Invest Ophthalmol Vis Sci. 44:4481–4488

    Article  PubMed  Google Scholar 

  • Klein R, Peto T, Bird A et al (2004) The epidemiology of age-related macular degeneration Am J Ophthalmol. 137:486–495

    Google Scholar 

  • Klein RJ, Zeiss C, Chew EY et al (2005) Complement factor H polymorphism in age-related macular degeneration. Science. 308:385–389

    Article  PubMed  CAS  Google Scholar 

  • 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. Neuroimage

    Google Scholar 

  • 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. 49:2376–2383

    Article  PubMed  Google Scholar 

  • 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. 51:1151–1163

    Article  PubMed  Google Scholar 

  • 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. 95:6448–6453

    Article  PubMed  CAS  Google Scholar 

  • 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. 175:2099–2110

    Article  PubMed  CAS  Google Scholar 

  • 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. 116:378–385

    Article  PubMed  CAS  Google Scholar 

  • 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 14:835–846

    PubMed  CAS  Google Scholar 

  • 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. 49:5136–5143

    Article  PubMed  Google Scholar 

  • 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. 50:793–800

    Article  PubMed  Google Scholar 

  • Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 81:741–766

    PubMed  CAS  Google Scholar 

  • Seth A, Cui J, To E, et al (2008) Complement-associated deposits in the human retina. Invest Ophthalmol Vis Sci. 49:743–750

    Article  PubMed  Google Scholar 

  • 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. 113:1545–1554

    CAS  Google Scholar 

  • 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. 31:491–502

    Article  PubMed  CAS  Google Scholar 

  • Walsh DT, Montero RM, Bresciani LG et al (2002) Amyloïd-beta peptide is toxic to neurons in vivo via indirect mechanisms. Neurobiol Dis. 10:20–27

    Article  PubMed  CAS  Google Scholar 

  • 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. 220:119–128

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Yates JR, Sepp T, Matharu BK et al (2007) Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 357:553–561

    Article  PubMed  CAS  Google Scholar 

  • 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 115:2793–2800

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de Recherche des Cordeliers, Université Pierre et Marie Curie – Paris 6, UMRS 872, 15 rue de l’Ecole de Médecine, Paris, 75006, France

    Julien Bruban, Virginie Dinet & Frédéric Mascarelli

  2. Université Paris Descartes, UMRS 872, Paris, 75006, France

    Julien Bruban, Virginie Dinet & Frédéric Mascarelli

  3. INSERM, UMRS872, Paris, 75006, France

    Julien Bruban, Virginie Dinet & Frédéric Mascarelli

Authors
  1. Julien Bruban
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginie Dinet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frédéric Mascarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julien Bruban .

Editor information

Editors and Affiliations

  1. University of California, San Francisco, n/a, San Francisco, 94143, USA

    Matthew M. LaVail

  2. University of Oklahoma Health Sciences C, Oklahoma City, 73104, USA

    John D. Ash

  3. Health Science Center, Dean A. McGee Eye Inst., University of Oklahoma, Stanton L. Young Blvd. 608, OKLAHOMA CITY, 73104, Oklahoma, USA

    Robert E. Anderson

  4. Division of Ophthalmology, Cole Eye Institute at the Cleveland Clin, Euclid Ave. 9500, Cleveland, 44195, Ohio, USA

    Joe G. Hollyfield

  5. Experimental Ophthalmology, University of Zurich, ZURICH, 8091, Switzerland

    Christian Grimm

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this paper

Cite this paper

Bruban, J., Dinet, V., Mascarelli, F. (2012). The Role of Amyloid-β in Retinal Degeneration. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation