Advertisement

Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

  • Alessandro Iannaccone
  • Indira Neeli
  • Pratheebha Krishnamurthy
  • Nataliya I. Lenchik
  • Haibao Wan
  • Ivan C. Gerling
  • Dominic M. Desiderio
  • Marko Z. Radic
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 legal blindness among people over the age of 50. In recent years, a role for inflammation in the pathogenesis of both AMD in general and drusen in particular has been established at the biological, experimental, and genetic level. The purpose of this chapter is to (1) illustrate our rationale for the hypothesis that, in the aforementioned inflammatory context, auto-antibodies (auto-Abs) are biomarkers relevant to ocular disease status in AMD, based on a brief review of the literature; (2) present our preliminary data supporting this hypothesis from our ongoing investigations; and (3) propose a mechanistic framework for the formation of auto-Abs in AMD and their possible role in disease development and progression. Auto-Ab targets have the potential to be important disease biomarkers and may contribute significantly to AMD development and progression.

Keywords

Age-related macular degeneration Autoimmunity Inflammation Biomarkers Pathogenesis 

Notes

Acknowledgments

Supported by the International Retinal Research Foundation, NIH grants K23 EY000409 and R21 EY018416, and an unrestricted grant from Research to Prevent Blindness.

References

  1. Anderson DH, Radeke MJ, Gallo NB et al (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29:95–112PubMedCrossRefGoogle Scholar
  2. Cherepanoff S, Mitchell P, Wang JJ et al (2006) Retinal autoantibody profile in early age-related macular degeneration: preliminary findings from the Blue Mountains Eye Study. Clin Experiment Ophthalmol 34:590–595PubMedCrossRefGoogle Scholar
  3. Ebrahem Q, Renganathan K, Sears J et al (2006) Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration. Proc Natl Acad Sci U S A 103:13480–13484PubMedCrossRefGoogle Scholar
  4. Friedman DS, O’Colmain BJ, Munoz B et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572PubMedCrossRefGoogle Scholar
  5. Gehrs KM, Anderson DH, Johnson LV et al (2006) Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Ann Med 38:450–471PubMedCrossRefGoogle Scholar
  6. Gonzalez-Rey E, Delgado M (2005) Role of vasoactive intestinal peptide in inflammation and autoimmunity. Curr Opin Investig Drugs 6:1116–1123PubMedGoogle Scholar
  7. Grindle CFJ, Marshall J (1978) Ageing changes in Bruch’s membrane and their functional implications. Trans Ophthalmol Soc UK 98:172–175PubMedGoogle Scholar
  8. Grunwald JE, Metelitsina TI, Dupont JC et al (2005) Reduced foveolar choroidal blood flow in eyes with increasing AMD severity. Invest Ophthalmol Vis Sci 46:1033–1038PubMedCrossRefGoogle Scholar
  9. Grunwald JE, Hariprasad SM, DuPont J et al (1998) Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci 39:385–390PubMedGoogle Scholar
  10. Gu J, Pauer GJ, Yue X et al (2009) Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. Mol Cell Proteomics 8:1338–1349PubMedCrossRefGoogle Scholar
  11. Gu J, Pauer GJ, Yue X et al (2010) Proteomic and Genomic Biomarkers for Age-Related Macular Degeneration. Adv Exp Med Biol 664:411–417PubMedCrossRefGoogle Scholar
  12. Gu X, Sun M, Gugiu B et al (2003a) Oxidatively truncated docosahexaenoate phospholipids: total synthesis, generation, and peptide adduction chemistry. J Org Chem 68:3749–3761PubMedCrossRefGoogle Scholar
  13. Gu X, Meer SG, Miyagi M et al (2003b) Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration. J Biol Chem 278:42027–42035PubMedCrossRefGoogle Scholar
  14. Gurne DH, Tso MO, Edward DP et al (1991) Antiretinal antibodies in serum of patients with age-related macular degeneration. Ophthalmology 98:602–607PubMedGoogle Scholar
  15. Hageman GS, Luthert PJ, Victor Chong NH et al (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 20:705–732PubMedCrossRefGoogle Scholar
  16. Hawkins B, Bird A, Klein R et al (1999) Epidemiology of age-related macular degeneration. Mol Vis 5:26PubMedGoogle Scholar
  17. Hollyfield JG, Bonilha VL, Rayborn ME et al (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14:194–198PubMedCrossRefGoogle Scholar
  18. Jablonski MM, Iannaccone A, Reynolds DH et al (2007) Age-Related Decline in VIP-Positive Parasympathetic Nerve Fibers in the Human Submacular Choroid. Invest Ophthalmol Vis Sci 48:479–485PubMedCrossRefGoogle Scholar
  19. 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
  20. Killingsworth MC, Sarks SH (1982) Giant cells in discifiorm macular degeneration of the human eye. Micron 13:359–360Google Scholar
  21. Killingsworth MC, Sarks JP, Sarks SH (1990) Macrophages related to Bruch’s Membrane in Age-Related Macular Degeneration. Eye 4:613–621PubMedCrossRefGoogle Scholar
  22. Patel N, Ohbayashi M, Nugent AK et al (2005) Circulating anti-retinal antibodies as immune markers in age-related macular degeneration. Immunology 115:422–430PubMedCrossRefGoogle Scholar
  23. Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223:69–76PubMedCrossRefGoogle Scholar
  24. Penfold PL, Killingsworth MC, Sarks SH (1986) Senile macular degeneration. The involvement of giant cells in atrophy of the retinal pigment epithelium. Invest Ophthalmol Vis Sci 27:364–371Google Scholar
  25. Penfold PL, Provis JM, Furby JH et al (1990) Autoantibodies to retinal astrocytes associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 228:270–274PubMedCrossRefGoogle Scholar
  26. Pozo D, Gonzalez-Rey E, Chorny A et al (2007) Tuning immune tolerance with vasoactive intestinal peptide: a new therapeutic approach for immune disorders. Peptides 28:1833–1846PubMedCrossRefGoogle Scholar
  27. Smalley SG, Barrow PA, Foster N (2009) Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory disease. Clin Exp Immunol 157:225–234PubMedCrossRefGoogle Scholar
  28. Swaroop A, Branham KE, Chen W et al (2007) Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. Hum Mol Genet 16 Spec No. 2:R174-182Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Alessandro Iannaccone
    • 1
  • Indira Neeli
    • 1
    • 2
  • Pratheebha Krishnamurthy
    • 1
  • Nataliya I. Lenchik
    • 3
  • Haibao Wan
    • 4
  • Ivan C. Gerling
    • 3
  • Dominic M. Desiderio
    • 4
  • Marko Z. Radic
    • 2
  1. 1.Department of Ophthalmology, Hamilton Eye InstituteUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of Molecular SciencesUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.Department of Internal MedicineUniversity of Tennessee Health Science CenterMemphisUSA
  4. 4.Department of Neurology, Stout Mass Spectrometry LaboratoryUniversity of Tennessee Health Science CenterMemphisUSA

Personalised recommendations