The Pathophysiology of Cigarette Smoking and Age-Related Macular Degeneration

Dhubhghaill, S.S. Ni; Cahill, Mark; Campbell, Matthew; Cassidy, Lorraine; Humphries, Marian M.; Humphries, Pete

doi:10.1007/978-1-4419-1399-9_50

Cited by 40 publications

(27 citation statements)

References 63 publications

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“…These results suggest that these two polymorphisms are not independent markers of AMD occurrence and development. A number of previous findings revealed a relevant synergistic effect of genetic polymorphisms and tobacco smoking on AMD development (Chu et al 2008;Ayala-Haedo et al 2010;Lee et al 2010) and smoking is a major environmental risk factor for AMD, because chemicals contained in cigarette smoke can be involved in AMD pathogenesis in a number of ways (Dhubhghaill et al 2010). In the present study, the stratification of subjects regarding to smoking status revealed an association between the A allele of the -576G>A-TF polymorphism and AMD among smokers.…”

Section: Discussionsupporting

confidence: 58%

The A Allele of the -576G>A Polymorphism of the Transferrin Gene Is Associated with the Increased Risk of Age-Related Macular Degeneration in Smokers

Wysokiński

Szaflik

Sklodowska

et al. 2011

Tohoku J. Exp. Med.

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Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries, and its pathogenesis is underlined by genetic and environmental factors. Oxidative stress is a major environmental risk factor of AMD; namely, AMD is associated with the increased level of reactive oxygen species, which may be produced in reactions catalyzed by iron present in the retina. Therefore, variability of the genes of iron metabolism may be important in the AMD risk. In the present study, we analyzed the association between AMD and the -576G>A polymorphism of the transferrin gene or the 1892C>T polymorphism of the transferrin receptor 2 (TFR2) gene in 278 patients with AMD and 105 controls. The former polymorphism is located in the promoter region of the transferrin gene and may affect the level of its transcription, while the latter is a synonymous mutation in the exon 16, which may affect the efficiency of translation of TFR2 mRNA. Transferrin and TFR2 are important in iron homeostasis. The A allele of the -576A>G polymorphism was significantly associated with the increased risk of AMD in tobacco smokers, whereas the 1892C>T polymorphism did not influence the risk of AMD related to smoking. Moreover, each polymorphism does not influence the risk of AMD associated with age, sex or the family history of the disease. In conclusion, the A allele of the -576A>G polymorphism of the transferrin gene may increase the risk of AMD in smokers.Keywords: age-related macular degeneration; iron metabolism; transferrin gene; transferrin receptor; genetic polymorphism Tohoku J. Exp. Med., 2011, 223 (4), 253-261. © 2011 Tohoku University Medical Press Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly in developed countries (Gehrs et al. 2006). It is a complex disease affecting the macula, a central part of the retina, leading to the irreversible impairment of central vision (Ding et al. 2009). The frequency of AMD among adults aged more than 75 years exceeds 30% and is expected to increase due to an increasing life expectancy (Liutkeviciene et al. 2010). The early stage of AMD is characterized by druzen formation-a white-yellow deposits in Bruch's membrane under the retinal pigment epithelial (RPE) layer and photoreceptor cells. AMD can develop to one of two advanced forms: dry (atrophic) and wet (exudative, neovascular). Slowly progressing and more common dry AMD is characterized by the presence of an irregular area of depigmentation as a result of the loss of RPE cells and causes a gradual geographic atrophy of the retina. The main feature of wet AMD is choroidal neovascularization with leakage and bleeding, leading to irreversible damage of photoreceptors (Coleman et al. 2008).

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Section: Discussionsupporting

confidence: 58%

The A Allele of the -576G>A Polymorphism of the Transferrin Gene Is Associated with the Increased Risk of Age-Related Macular Degeneration in Smokers

Wysokiński

Szaflik

Sklodowska

et al. 2011

Tohoku J. Exp. Med.

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“…40 There are several mechanisms by which cigarette smoking negatively affects the retina: increased oxidative stress, lipid peroxidation, and platelet aggregation, as well as a reduction in the plasma high-density lipoprotein or antioxidant levels. 39,41 Cigarette smoking also causes inflammation by activating complement C3 and other inflammatory factors and by reducing the serum levels of complement factor H. 41 Finally, cigarette smoking may damage the choroidal vessels and diminish choroidal blood flow, thereby causing chronic vasoconstriction. 39 In view of these data, it may not be surprising that chronic smoking was also an important risk factor for electrophysiological dysfunction of the retina in our study.…”

Section: Discussionmentioning

confidence: 99%

Effect of carotid endarterectomy on retinal function in 'asymptomatic' patients with hemodynamically significant carotid artery stenosis

Machalińska¹,

Kowalska-Budek²,

Kawa³

et al. 2017

Polish Archives of Internal Medicine

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“…Moreover, both AMD onset and disease progression are strongly influenced by smoking 62 . Epidemiologic studies of AMD suggest that the RPE is a specific target of cigarette smokeinduced injury.…”

Section: Light Exposure Of Photosensitizers and Cigarette Smokingmentioning

confidence: 99%

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Chiras

Kitsos

Petersen

et al. 2014

Critical Reviews in Clinical Laboratory Sciences

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Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

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The Pathophysiology of Cigarette Smoking and Age-Related Macular Degeneration

Cited by 40 publications

References 63 publications

The A Allele of the -576G>A Polymorphism of the Transferrin Gene Is Associated with the Increased Risk of Age-Related Macular Degeneration in Smokers

The A Allele of the -576G>A Polymorphism of the Transferrin Gene Is Associated with the Increased Risk of Age-Related Macular Degeneration in Smokers

Effect of carotid endarterectomy on retinal function in 'asymptomatic' patients with hemodynamically significant carotid artery stenosis

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

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