Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

Suñer, Iván J.; Espinosa‐Heidmann, Diego G.; Marin‐Castaño, Maria E.; Hernandez, E.; Pereira‐Simon, Simone; Cousins, Scott W.

doi:10.1167/iovs.03-0733

Cited by 129 publications

(96 citation statements)

References 47 publications

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“…7 It is postulated that smoking affects the pathogenesis of AMD by a variety of methods including promoting oxidative damage, inducing angiogenesis, impairing the choroidal circulation, and by activating the immune system including complement pathway. [8][9][10][11][12][13] Stopping smoking reduces the risk of AMD and after 20 years of cessation the risk of developing AMD is the same as for non-smokers. 14 In the last few years, the genetic factors significantly contributing to AMD risk have been identified.…”

Section: Introductionmentioning

confidence: 99%

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Rennie

Stinge

King

et al. 2011

Eye

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Aims Smoking can increase the risk of macular degeneration and this is more than additive if a person also has a genetic risk. The purpose of this study was to examine whether knowledge of genetic risk for age-related macular degeneration (AMD) could influence motivation to quit smoking. Methods A questionnaire-based study of hypothetical case scenarios given to 49 smokers without AMD. Participants were randomly allocated to a generic risk, high genetic risk, or low genetic risk of developing AMD scenario. Results Forty-seven percent knew of the link between smoking and eye disease. In all, 76%, 67%, and 46% for the high risk, generic, and low risk groups, respectively, would rethink quitting (P for trend ¼ 0.082). In all, 67%, 40%, and 38.5%, respectively, would be likely, very likely, or would definitely quit in the following month (P for trend ¼ 0.023). Few participants (o16% of any group) were very likely to or would definitely attend a quit smoking session with no difference across groups. In all, 75.5% of participants would consider taking a genetic test for AMD. Conclusion In this pilot study, a trend was seen for the group given high genetic risk information to be more likely to quit than the generic or low genetic risk groups. Participants were willing to take a genetic test but further work is needed to address the cost benefits of routine genetic testing for risk of AMD. More generic risk information should be given to the public, and health warnings on cigarette packets that 'smoking causes blindness' is a good way to achieve this.

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Section: Introductionmentioning

confidence: 99%

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Rennie

Stinge

King

et al. 2011

Eye

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“…MMP-2 and MMP-9 are the two major enzymes that can selectively degrade type IV collagen and facilitate tumor invasion and metastasis in various experimental models, including gastric, colon, and breast cancers (19)(20)(21). Administration of nicotine increased the severity of choroidal neovascularization and also reversed the VEGF-induced suppression of MMP-2 activity in mice (22), showing that MMP could play a role in the angiogenesis induced by nicotine. Indeed, suppression of MMP by different inhibitors markedly reduced tumor cell invasiveness and metastasis (23).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Shin¹,

Wu²,

Chu³

et al. 2005

Molecular Cancer Research

106

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Blockade of angiogenesis is a promising strategy to suppress tumor growth, invasion, and metastasis. Vascular endothelial growth factor (VEGF), which binds to tyrosine kinase receptors [VEGF receptors (VEGFR) 1 and 2], is the mediator of angiogenesis and mitogen for endothelial cells. Cyclooxygenase-2 (COX-2) plays an important role in the promoting action of nicotine on gastric cancer growth. However, the action of nicotine and the relationship between COX-2 and VEGF/VEGFR system in tumorigenesis remain undefined. In this study, the effects of nicotine in tumor angiogenesis, invasiveness, and metastasis were studied with sponge implantation and Matrigel membrane models. Nicotine (200 Mg/mL) stimulated gastric cancer cell proliferation, which was blocked by SC-236 (a highly selective COX-2 inhibitor) and CBO-P11 (a VEGFR inhibitor). This was associated with decreased VEGF levels as well as VEGFR-2 but not VEGFR-1 expression. Topical injection of nicotine enhanced tumor-associated vascularization, with a concomitant increase in VEGF levels in sponge implants. Again, application of SC-236 (2 mg/kg) and CBO-P11 (0.4 mg/kg) partially attenuated vascularization by f30%. Furthermore, nicotine enhanced tumor cell invasion through the Matrigel membrane by 4-fold and promoted migration of human umbilical vein endothelial cells in a cocultured system with gastric cancer cells. The activity of matrix metalloproteinases 2 and 9 and protein expressions of plasminogen activators (urokinase-type plasminogen activator and its receptor), which are the indicators of invasion and migration processes, were increased by nicotine but blocked by COX-2 and VEGFR inhibitors. Taken together, our results reveal that the promoting action of nicotine on angiogenesis, tumor invasion, and metastasis is COX-2/VEGF/VEGFR dependent. (Mol Cancer Res 2005;3(11):607 -15)

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“…Both 11-Z-and 9-Z-retinoids are metabolic intermediates in vision and gene regulation, respectively, and strict homeostatic control is essential for proper function. Although oxidative stress and nicotine receptor activation may also play a role in the development of tobaccoassociated pathologies (36), the discovery that a nicotine metabolite catalyzes the isomerization of Z-retinals to all-E-retinal provides chemical evidence for an unrecognized mechanism of smoking toxicity. Specifically, the accumulation of all-E-retinal feeds the A2E biosynthetic pathway and leads to lipofuscin of RPE cells and ultimately age-related macular degeneration.…”

Section: Resultsmentioning

confidence: 99%

“…Although recent genomic studies have shown that a genetic predisposition for age-related macular degeneration is manifested in complement factor H polymorphisms (30)(31)(32), the primary environmental factor contributing to age-related macular degeneration is cigarette smoking (33)(34)(35). Indeed, mice administered nicotine as a dietary supplement were shown to have an increased incidence of age-related macular degeneration (36).…”

mentioning

confidence: 99%

Altered retinoid homeostasis catalyzed by a nicotine metabolite: Implications in macular degeneration and normal development

Brogan

Dickerson

Boldt

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Retinoids (vitamin A) serve two distinct functions in higher animals: light absorption for vision and gene regulation for growth and development. Cigarette smoking is a contributing factor for diseases that affect vision such as age-related macular degeneration and increases the risk of birth defects; however, altered retinoid homeostasis has received little attention as a potential mechanism for smoking-associated toxicities. Herein, we demonstrate that nornicotine, a nicotine metabolite and component of cigarette smoke, catalyzes the Z-to-E alkene isomerization of unsaturated aldehydes and ketones, including retinals. Despite the recent explosion in the use of organic compounds as chemical catalysts, minimal effort has been devoted to biologically relevant organocatalysis. Our study demonstrates a system in which a lowest unoccupied molecular orbital-lowering intermediate similar to the endogenous protein rhodopsin effectively catalyzes isomerization under biologically relevant conditions. The product of retinal isomerization is all-E-retinal, which in the eye is a biosynthetic precursor to N-retinylidene-N-retinylethanolamine, a hallmark of age-related macular degeneration. Furthermore, 9-Z-and all-E-retinal isomers are biosynthetic precursors to 9-Z-and all-Eretinoic acids, ligands that mediate specific cellular responses by binding to transcriptional regulatory proteins critical in growth and development. Strict maintenance of retinal isomer composition is essential for proper transcriptional regulation. Nornicotinecatalyzed retinal isomerization implies an underlying molecular mechanism for age-related macular degeneration, the birth defects associated with smoking, and other smoking-associated abnormalities that stem from disruption of retinoid metabolism.organocatalysis ͉ retinal isomerization V itamin A (all-E-retinol) and provitamin A carotenoids are metabolized into key retinoid intermediates that play a critical role in vision, bone growth, reproduction, cell division, and cell differentiation (1-4). These essential nutrients also help to prevent infection by maintaining the integrity of the skin and mucous membranes (5-8). Furthermore, vitamin A assists in the regulation of the immune system by stimulating lymphocyte production (2, 4, 6, 9). Retinoids are involved in numerous physiological functions, and the molecular processes can be divided into two main categories. In vision, 11-Z-retinal is the essential light-absorbing component of the protein rhodopsin, whereas all other nonvisual cellular responses are thought to be mediated by ligand activation of transcriptional regulatory proteins ( Fig. 1) (10, 11).In the visual cycle, all-E-retinol is converted to 11-Z-retinal through a multistep enzymatic process. The photoreceptor protein rhodopsin is an iminium-ion complex of 11-Z-retinal and a lysine residue of the protein opsin. Complexation effectively lowers the lowest unoccupied molecular orbital of 11-Z-retinal and allows for isomerization to all-E-retinal when rhodopsin absorbs a photon of ligh...

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Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

Cited by 129 publications

References 47 publications

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Altered retinoid homeostasis catalyzed by a nicotine metabolite: Implications in macular degeneration and normal development

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