Nicotine Increases the VEGF/PEDF Ratio in Retinal Pigment Epithelium: A Possible Mechanism for CNV in Passive Smokers with AMD

Pons, Marianne; Marin‐Castaño, Maria E.

doi:10.1167/iovs.10-6254

Cited by 65 publications

(49 citation statements)

References 86 publications

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“…48,49 Similarly we observed a strong correlation between increased pack-years and a history of choroidal neovascularization in fellow eyes of those with chronic tobacco smoke exposure, indicating a dose-dependent increased risk of late AMD in smokers. Smoking has also been associated with increased risk of polypoidal choroidal vasculopathy (PCV), a process typically demonstrating a thicker than normal choroid.…”

Section: Discussionsupporting

confidence: 55%

Smoking and choroidal thickness in patients over 65 with early-atrophic age-related macular degeneration and normals

Sigler

Randolph

Calzada

et al. 2014

Eye

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Objective To compare macular choroidal thickness between cigarette smokers, those with a history of smoking, and nonsmokers in patients over 65 years of age with earlyatrophic age-related macular degeneration (AMD) and normals. Methods Prospective, consecutive, observational case series. Enhanced depth imaging spectral domain optical coherence tomography 12-line radial scans were performed and choroidal thickness manually quantified at 84 points in the central 3 mm of the macula. Data of normals, soft drusen alone, and soft drusen with additional features of early AMD were compared. A multivariate analysis of variance (MANOVA) model, controlling for age, was constructed to evaluate the effect of smoking history and AMD features on choroidal thickness. Results A history of smoking was significantly associated with a thinner choroid across all patients via logistic regression (P ¼ 0.004; O.R. ¼ 12.4). Mean macular choroidal thickness was thinner for smokers (148±63 mm) than for nonsmokers (181±65 mm) among all diagnosis categories (P ¼ 0.003). Subgroup analysis of patients with AMD features revealed a similar decreased choroidal thickness in smokers (121 ± 41 mm) compared with nonsmokers (146 ± 46 mm, P ¼ 0.006). Bivariate analysis revealed an association between increased pack-years of smoking and a thin choroid across all patients (Po0.001) and among patients with features of early AMD (Po0.001). Both the presence of features of macular degeneration (Po0.001) and a history of smoking (P ¼ 0.024) were associated with decreased choroidal thickness in a MANOVA model. ConclusionChronic cigarette smoke exposure may be associated with decreased choroidal thickness. There may be an anatomic sequelae to chronic tobacco smoke exposure that underlies previously reported AMD risk.

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Section: Discussionsupporting

confidence: 55%

Smoking and choroidal thickness in patients over 65 with early-atrophic age-related macular degeneration and normals

Sigler

Randolph

Calzada

et al. 2014

Eye

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“…Our observation is not only consistent with these results, but also demonstrated that nornicotine had a similar impact on this type of cells. The mechanism for the ARPE-19 cells' resistance to nornicotine and NT treatment is not clear, but it may be related to different subunits of nicotinic cholinergic receptors in RPE cells [5,17]. In our experiment, cell viability was compromised with the incubation of either 100 μ M nornicotine or 100 μ M NT in ARPE-19 cells and HUVECs.…”

Section: Discussionmentioning

confidence: 77%

“…The wet form is characterized by the growth of leaky new abnormal blood vessels that originate from the subjacent choroid through Bruch's membrane into the subretinal pigment epithelium (RPE) and subretinal space. The choroidal neovascularization (CNV) can cause bleeding and fluid leakage, which along with RPE and photoreceptor destruction lead to rapid vision loss [5]. …”

Section: Introductionmentioning

confidence: 99%

“…Although previous studies have reported that NT stimulates vascular endothelial growth factor (VEGF) expression in some kinds of cells, including RPE and endothelial cells [5,18,19], there are few reports about the role of nornicotine, the main metabolite of nicotine, in angiogenesis. In our study, the proangiogenic effects of nornicotine and NT in angiogenesis were characterized and compared.…”

Section: Introductionmentioning

confidence: 99%

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Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio

Zhang¹,

Wang³

et al. 2015

Ophthalmic Res

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Purpose: The purpose of the current study was to evaluate the influences of nornicotine and nicotine (NT) in cigarette smoke on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelium cells and human umbilical vein endothelial cells (HUVECs). Furthermore, the angiogenic behaviors of endothelial cells under nornicotine and NT treatment were assessed by using in vitro methods. Methods: ARPE-19 cells and HUVECs were treated with different concentrations of either nornicotine or NT for different periods of time. The cell proliferative effect was investigated by using the method of MTT analysis. HUVEC migration and tube formation were assessed by using the scratch assay and Matrigel models. The expressions of VEGF and PEDF gene and protein in both types of cells were examined by real-time RT-PCR and Western blot. Results: There was no proliferation of ARPE-19 cells following treatment with various concentrations of nornicotine or NT. In contrast, nornicotine or NT significantly stimulated HUVEC proliferation, migration and tube formation. Nornicotine and NT upregulated the expression of VEGF but suppressed the expression of PEDF at both mRNA and protein levels in a dose- and time-dependent manner in ARPE-19 cells and HUVECs. Conclusions: Our results demonstrate that nornicotine and NT promoted endothelial cellular proliferation, migration and tube formation of HUVECs in vitro. These effects might be partly due to simultaneous modulation of VEGF/PEDF signaling in ARPE-19 cells and HUVECs.

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“…This is beneficial in improving retinal hypoxia caused by DR. PEDF is a natural antagonist for VEGF. [21][22][23] The retinas of normal rats had higher expression of PEDF than diabetic rats, and pharmacologic vitreolysis-induced complete PVD could increase the expression of PEDF. The ratio of endothelial cells to pericytes can reflect angiogenesis of the retina.…”

Section: Discussionmentioning

confidence: 99%

Enzyme-Induced Vitreolysis Can Alleviate the Progression of Diabetic Retinopathy Through the HIF-1α Pathway

Zhang

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Li C, Chen P, Zhang J, et al. Enzyme-induced vitreolysis can alleviate the progression of diabetic retinopathy through the HIF-1a pathway. Invest Ophthalmol Vis Sci. 2013;54:4964-4970. DOI:10.1167/ iovs.12-11443 PURPOSE. We studied the mechanism by which complete posterior vitreous detachment by enzyme-induced vitreolysis alleviates the progression of diabetic retinopathy. METHODS.We enrolled 50 diabetic rats and 20 normal control rats in this study. The right eyes of these diabetic rats were treated with a hyaluronidase (5 U) plus plasmin (0.25 U) by intravitreous injection (ET group), while the left eyes of diabetic rats (DR group) and eyes of the normal rats (NC group) were injected with balanced saline. Eight months after intravitreous injection, the oxygen concentration in the vitreous was measured, and the expression levels of hypoxia inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), and basic fibroblast growth factor (bFGF) in retinas were determined by real-time PCR and Western blot. Clinical observation, visual electrophysiology tests, and scanning electron microscopy (SEM) also were performed on the rats.RESULTS. SEM results showed that the surface of retinas in the ET group had little vitreous cortex and the inner limiting membrane could be observed. The oxygen concentration of the midvitreous was higher in the ET group than other groups. A significantly high expression of HIF-1a, VEGF, and bFGF was detected in the retinas of the DR group compared to the ET and NC groups. In visual electrophysiology tests, amplitude decline and peak time latency were found in diabetic rats, and changes in the DR group were more obvious than in the ET group.CONCLUSIONS. Enzyme-induced vitreolysis can increase oxygen concentration in the vitreous, with reduced expression of HIF-1a, VEGF, and bFGF, and increased expression of PEDF in the retinas, thus alleviating the progression of diabetic retinopathy.

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Nicotine Increases the VEGF/PEDF Ratio in Retinal Pigment Epithelium: A Possible Mechanism for CNV in Passive Smokers with AMD

Abstract: NT increased the VEGF-to-PEDF ratio in the RPE through nAchR in vitro and in vivo. This alteration in the ratio may play a key role in the progression to wet AMD in passive smokers.

Cited by 65 publications

References 86 publications

Smoking and choroidal thickness in patients over 65 with early-atrophic age-related macular degeneration and normals

Smoking and choroidal thickness in patients over 65 with early-atrophic age-related macular degeneration and normals

Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio

Enzyme-Induced Vitreolysis Can Alleviate the Progression of Diabetic Retinopathy Through the HIF-1α Pathway

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