title: Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration.
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.
authors.affiliation: Forsythe Laboratory for the Investigation of the Aging Retina, Department of Ophthalmology, Northwestern University School of Medicine, Chicago, Illinois, United States of America. a-wang@northwestern.edu
authors.forename: Ai Ling
authors.initials: AL
authors.lastname: Wang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lukas
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.forename: Nga
authors.initials: N
authors.lastname: Du
authors.forename: James T
authors.initials: JT
authors.lastname: Handa
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Neufeld
mesh_terms: D000367:Age Factors; D000818:Animals; D016570:Bruch Membrane / Q000378:metabolism; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D004272:DNA, Mitochondrial