Skip to main content
Article thumbnail
Location of Repository

Changes in Retinal Pigment Epithelium Related to Cigarette Smoke: Possible Relevance to Smoking as a Risk Factor for Age-Related Macular Degeneration

By Ai Ling Wang, Thomas J. Lukas, Ming Yuan, Nga Du, James T. Handa and Arthur H. Neufeld

Abstract

Age-related Macular Degeneration (AMD) is a major cause of central vision loss in the elderly and smoking is a primary risk factor associated with the prevalence and incidence of AMD. To better understand the cellular and molecular bases for the association between smoking and AMD, we determined the effects of Benzo(a)Pyrene (B(a)P), a toxic element in cigarette smoke, on cultured retinal pigment epithelia (RPE) and we examined the RPE/choroid from mice exposed to chronic cigarette smoke. We measured: mitochondrial DNA (mtDNA) damage, phagocytic activity, lysosomal enzymes, exosome markers and selected complement pathway components. In the presence of a non-cytotoxic dose of B(a)P, there was extensive mtDNA damage but no nuclear DNA damage. RPE phagocytic activity was not altered but there were increased lysosomal activity, exocytotic activity and complement pathway components. Retinas from mice exposed to cigarette smoke contained markers for mtDNA damage, exosomes and complement pathway components surrounding Bruch's membrane. Markers for these processes are found in drusen from AMD patients. Thus, smoking may cause damage to mtDNA and increased degradative processes in the RPE. These altered cell biological processes in the RPE may contribute to the formation of drusen in individuals who are cigarette smokers and underlie susceptibility to genetic mutations associated with AMD

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2669185
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2005). 28,000 Cases of age related macular degeneration causing visual loss in people aged 75 years and above in the United Kingdom may be attributable to smoking.
    2. (2005). A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.
    3. (2007). A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration.
    4. (1997). Age-related increase in activity of specific lysosomal enzymes in the human retinal pigment epithelium.
    5. (2008). Age-related increase in mitochondrial DNA damage and loss of DNA repair capacity in the neural retina. Neurobiol Aging.
    6. (1996). Agerelated changes of glycosidases in human retinal pigment epithelium.
    7. (2008). Agerelated macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA.
    8. (1996). ARPE-19, a human retinal pigment epithelial cell line with differentiated properties.
    9. (2008). Autophagy and exosomes in the aged retinal pigment epithelium: Possible relevance to drusen formation and age-related macular degeneration. PLoS ONE.
    10. (2008). Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice.
    11. (2006). Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration.
    12. (1999). Distribution of cathepsin D in human eyes with or without age-related maculopathy.
    13. (2009). Dysfunction of the retinal pigment epithelium with age: increased iron decreases phagocytosis and lysosomal activity. Invest Ophthalmol Vis Sci.
    14. (2006). Exosomes: a common pathway for a specialized function.
    15. (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.
    16. (2000). Genetic association of manganese superoxide dismutase with exudative agerelated macular degeneration.
    17. (2005). Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk.
    18. (2008). Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid.
    19. (1982). Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons:
    20. (1999). Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage.
    21. (1980). Mitochondrial DNA is a major cellular target for a dihydrodiol-epoxide derivative of benzo[a]pyrene.
    22. (2008). Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration.
    23. (2008). Molecular pathology of age-related macular degeneration. Prog Retin Eye Res.
    24. (1987). Peripherin. A rim-specific membrane protein of rod outer segment discs.
    25. (2004). Prevalence of age-related macular degeneration in the United States.
    26. (1994). Regional variation and age-related changes of lysosomal enzymes in the human retinal pigment epithelium.
    27. (2002). Retinal pigment epithelial cell DNA is damaged by exposure to benzo[a]pyrene, a constituent of cigarette smoke.
    28. (2004). Risk factors for incident age-related macular degeneration: pooled findings from 3 continents.
    29. (2005). Risk factors for the incidence of
    30. (2006). Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation.
    31. (2005). Smoking and age-related macular degeneration: a review of association.
    32. (2002). Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains Eye Study.
    33. (2007). Tetraspanin CD81 is required for the alpha v beta5-integrin-dependent particle-binding step of RPE phagocytosis.
    34. (2008). The aged retinal pigment epithelium/choroid: a potential substratum for the pathogenesis of age-related macular degeneration.
    35. (2006). Variation in factor B (BF) and complement component 2 (C2) genes is associated with agerelated macular degeneration.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.