Skip to main content
SpringerLink
Log in
Book cover

Retinal Degenerative Diseases pp 51–59Cite as

Exploring the Potential Role of the Oxidant-Activated Transcription Factor Aryl Hydrocarbon Receptor in the Pathogenesis of AMD

  • Conference paper
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 723))

Abstract

Cigarette smoking is the most consistently shown risk factor associated with progression of all forms of age-related macular degeneration. The signaling pathways activated by cigarette smoke oxidants have not been fully elucidated. Herein, we review the effect of oxidant injury in retinal pigment epithelial cells at the subcellular level, introduce an oxidant-activated transcription factor called aryl hydrocarbon receptor, and discuss mechanisms by which this receptor may regulate the oxidative stress response in RPE cells and disease.

This is a preview of subscription content, 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

Learn about institutional subscriptions

References

  • Alcazar O, Hawkridge AM, Collier TS et al (2009) Proteomic characterization of cell membrane blebs in human retinal pigment epithelium cells. Mol Cell Proteomics

    Google Scholar 

  • Aly HA, Domenech O (2009) Cytotoxicity and mitochondrial dysfunction of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in isolated rat hepatocytes. Toxicol Lett 191:79–87

    Article  PubMed  CAS  Google Scholar 

  • Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol 48:257–293

    Article  PubMed  Google Scholar 

  • Bird AC, Bressler NM, Bressler SB et al (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 39:367–374

    Article  PubMed  CAS  Google Scholar 

  • Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ (2000) Role of quinones in toxicology. Chem Res Toxicol 13:135–160

    Article  PubMed  CAS  Google Scholar 

  • Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    Article  PubMed  CAS  Google Scholar 

  • Canter JA, Olson LM, Spencer K et al (2008) Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration. PLoS ONE 3:e2091

    Article  PubMed  Google Scholar 

  • Chomyn A, Attardi G (2003) MtDNA mutations in aging and apoptosis. Biochem Biophys Res Commun 304:519–529

    Article  PubMed  CAS  Google Scholar 

  • Ciulla TA, Rosenfeld PJ (2009) Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. Curr Opin Ophthalmol 20:158–165

    Article  PubMed  Google Scholar 

  • Coleman HR, Chan CC, Ferris FL, 3 rd, Chew EY (2008) Age-related macular degeneration. Lancet 372:1835–1845

    Article  PubMed  CAS  Google Scholar 

  • Dalton TP, Puga A, Shertzer HG (2002) Induction of cellular oxidative stress by aryl hydrocarbon receptor activation. Chem Biol Interact 141:77–95

    Article  PubMed  CAS  Google Scholar 

  • Dewan A, Liu M, Hartman S et al (2006) HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 314:989–992

    Article  PubMed  CAS  Google Scholar 

  • Diani-Moore S, Papachristou F, Labitzke E, Rifkind AB (2006) Induction of CYP1A and cyp2-mediated arachidonic acid epoxygenation and suppression of 20-hydroxyeicosatetraenoic acid by imidazole derivatives including the aromatase inhibitor vorozole. Drug Metab Dispos 34:1376–1385

    Article  PubMed  CAS  Google Scholar 

  • Edwards AO, Ritter R, 3 rd, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424

    Article  PubMed  CAS  Google Scholar 

  • Espinosa-Heidmann DG, Suner IJ, Catanuto P et al (2006) Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD. Invest Ophthalmol Vis Sci 47:729–737

    Article  PubMed  Google Scholar 

  • Feher J, Kovacs I, Artico M et al (2006) Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging 27:983–993

    Article  PubMed  CAS  Google Scholar 

  • Fiotti N, Pedio M, Battaglia Parodi M et al (2005) MMP-9 microsatellite polymorphism and ­susceptibility to exudative form of age-related macular degeneration. Genet Med 7:272–277

    Article  PubMed  CAS  Google Scholar 

  • Friedman DS, O’Colmain BJ, Munoz B et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572

    Article  PubMed  Google Scholar 

  • Fritsche LG, Loenhardt T, Janssen A et al (2008) Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet 40:892–896

    Article  PubMed  CAS  Google Scholar 

  • Godley BF, Shamsi FA, Liang FQ et al (2005) Blue light induces mitochondrial DNA damage and free radical production in epithelial cells. J Biol Chem 280:21061–21066

    Article  PubMed  CAS  Google Scholar 

  • Hageman GS 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 

  • Hankinson O (1995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340

    Article  PubMed  CAS  Google Scholar 

  • Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479

    Article  PubMed  CAS  Google Scholar 

  • Imamura Y, Noda S, Hashizume K et al (2006) Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci U S A 103:11282–11287

    Article  PubMed  CAS  Google Scholar 

  • Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358:2606–2617

    Article  PubMed  CAS  Google Scholar 

  • Jarrett S, Lin H, Godley B, Boulton M (2008) Mitochondrial DNA damage and its potential role in retinal degeneration. Prog Retin Eye Res 27:596–607

    Article  PubMed  CAS  Google Scholar 

  • Jia L, Liu Z, Sun L et al (2007) Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. Invest Ophthalmol Vis Sci 48:339–348

    Article  PubMed  Google Scholar 

  • Karchner SI, Jenny MJ, Tarrant AM et al (2009) The active form of human aryl hydrocarbon receptor (AHR) repressor lacks exon 8, and its Pro 185 and Ala 185 variants repress both AHR and hypoxia-inducible factor. Mol Cell Biol 29:3465–3477

    Article  PubMed  CAS  Google Scholar 

  • Kasahara E, Lin LR, Ho YS, Reddy VN (2005) SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment epithelium: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci 46:3426–3434

    Article  PubMed  Google Scholar 

  • Klein R, Knudtson MD, Cruickshanks KJ, Klein BE (2008) Further observations on the association between smoking and the long-term incidence and progression of age-related macular degeneration: the Beaver Dam Eye Study. Arch Ophthalmol 126:115–121

    Article  PubMed  Google Scholar 

  • Klein R, Klein BE, Knudtson MD et al (2007) Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114:253–262

    Article  PubMed  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 

  • Landreth G, Jiang Q, Mandrekar S, Heneka M (2008) PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 5:481–489

    Article  PubMed  CAS  Google Scholar 

  • Lenaz G (1998) Role of mitochondria in oxidative stress and ageing. Biochim Biophys Acta 1366:53–67

    Article  PubMed  CAS  Google Scholar 

  • Liang FQ, Godley BF (2003) Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res 76:397–403

    Article  PubMed  CAS  Google Scholar 

  • Marin-Castano ME, Striker GE, Alcazar O, Catanuto P, Espinosa-Heidmann DG, Cousins SW (2006) Repetitive nonlethal oxidant injury to retinal pigment epithelium decreased extracellular matrix turnover in vitro and induced sub-RPE deposits in vivo. Invest Ophthalmol Vis Sci 47:4098–4112

    Article  PubMed  Google Scholar 

  • Niki E, Minamisawa S, Oikawa M, Komuro E (1993) Membrane damage from lipid oxidation induced by free radicals and cigarette smoke. Ann N Y Acad Sci 686:29–37. discussion 37–28

    Article  PubMed  CAS  Google Scholar 

  • Ohtake F, Baba A, Takada I et al (2007) Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446:562–566

    Article  PubMed  CAS  Google Scholar 

  • Pollenz RS (2002) The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation. Chem Biol Interact 141:41–61

    Article  PubMed  CAS  Google Scholar 

  • Polster BM, Fiskum G (2004) Mitochondrial mechanisms of neural cell apoptosis. J Neurochem 90:1281–1289

    Article  PubMed  CAS  Google Scholar 

  • Pryor WA (1997) Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Health Perspect 105 Suppl 4:875–882

    Article  PubMed  CAS  Google Scholar 

  • Rifkind AB (2006) CYP1A in TCDD toxicity and in physiology-with particular reference to CYP dependent arachidonic acid metabolism and other endogenous substrates. Drug Metab Rev 38:291–335

    Article  PubMed  CAS  Google Scholar 

  • Robinson E, Grieve DJ (2009) Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease. Pharmacol Ther 122:246–263

    Article  PubMed  CAS  Google Scholar 

  • Ross RJ, Bojanowski CM, Wang JJ et al (2007) The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci 48:1128–1132

    Article  PubMed  Google Scholar 

  • Schmidt S, Haines JL, Postel EA et al (2005) Joint effects of smoking history and APOE genotypes in age-related macular degeneration. Mol Vis 11:941–949

    PubMed  CAS  Google Scholar 

  • Schmidt S et al (2002) A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy. Ophthalmic Genet 23:209–223

    Article  PubMed  Google Scholar 

  • Seddon JM, George S, Rosner B (2006) Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Arch Ophthalmol 124:995–1001

    Article  PubMed  CAS  Google Scholar 

  • Senft AP, Dalton TP, Nebert DW et al (2002) Mitochondrial reactive oxygen production is dependent on the aromatic hydrocarbon receptor. Free Radic Biol Med 33:1268–1278

    Article  PubMed  CAS  Google Scholar 

  • Wang K, Wan YJ (2008) Nuclear receptors and inflammatory diseases. Exp Biol Med (Maywood) 233:496–506

    Article  CAS  Google Scholar 

  • Wang Z, Yang H, Ramesh A et al (2009) Overexpression of Cu/Zn-superoxide dismutase and/or catalase accelerates benzo(a)pyrene detoxification by upregulation of the aryl hydrocarbon receptor in mouse endothelial cells. Free Radic Biol Med 47:1221–1229

    Article  PubMed  CAS  Google Scholar 

  • Winston GW, Church DF, Cueto R, Pryor WA (1993) Oxygen consumption and oxyradical production from microsomal reduction of aqueous extracts of cigarette tar. Arch Biochem Biophys 304:371–378

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Camp NJ, Sun H et al (2006) A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science 314:992–993

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the American Health Assistance Foundation (GM) and Research to Prevent Blindness.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Duke University, Durham, NC, 27701, USA

    Goldis Malek

  2. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, 27701, USA

    Mary Dwyer & Donald McDonnell

Authors
  1. Goldis Malek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary Dwyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donald McDonnell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Goldis Malek .

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

Malek, G., Dwyer, M., McDonnell, D. (2012). Exploring the Potential Role of the Oxidant-Activated Transcription Factor Aryl Hydrocarbon Receptor in the Pathogenesis of AMD. 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_8

Download citation

Publish with us

Policies and ethics

Search

Navigation