Nicotine reduces VEGF-secretion and phagocytotic activity in porcine RPE

Klettner, Alexa; Doths, Johanna; Roider, Johann

doi:10.1007/s00417-011-1776-8

Cited by 13 publications

(12 citation statements)

References 39 publications

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“…Previous studies showed no significant growth of either primary RPE cells or ARPE-19 cells in response to 24-hour to 7-day NT treatment [25,26]. Our observation is not only consistent with these results, but also demonstrated that nornicotine had a similar impact on this type of cells.…”

Section: Discussionsupporting

confidence: 93%

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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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Section: Discussionsupporting

confidence: 93%

“…Increased VEGF expression and decreased PEDF expression has been reported in wet AMD-associated CNV membranes [27]. The RPE cells are known to secrete a variety of growth factors, such as VEGF, PEDF and platelet-derived growth factor [25,28]. Thus, RPE cells play a pivotal role in the support of the retina and choriocapillaris integrity.…”

Section: Discussionmentioning

confidence: 99%

Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio

Zhang¹,

Wang³

et al. 2015

Ophthalmic Res

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“…Neither low (10 nM) nor high concentration (10 mM) of nicotine treatment for 1–7 days affects RPE cell viability, proliferation or apoptosis 11–14 . Instead, exposure of 1 µM nicotine for 3 days changes RPE morphology 11 , whereas exposure of 100 µM nicotine for 7 days reduces the phagocytotic ability of the RPE 14 . Besides, nicotine would also reduce the expression of IL-8, PEDF, MMP2 and MMP9 11, 13 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, one-day treatment of 10 or 0.1 mM nicotine did not affect ARPE-19 cell viability or caspase-3/7 activity 13 . Furthermore, nicotine (1, 10 or 100 µM) did not induce cell death in porcine RPE during the 7-day treatment, but decreased VEGF secretion and reduced the phagocytotic ability of the RPE 14 .…”

Section: Introductionmentioning

confidence: 90%

Disruption of retinal pigment epithelial cell properties under the exposure of cotinine

Zhang

Brelén

et al. 2017

Sci Rep

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Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1–2 µM of nicotine and/or cotinine for 7 days. RPE cells treated with 2 μM cotinine and nicotine-cotinine mixture has lower MTT signals without significant changes in cell apoptosis or integrity. Moreover, RPE cell migration was retarded under cotinine treatments, but not nicotine. Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells. In addition, cotinine and nicotine-cotinine mixture suppressed VEGF and IL-8 expression and upregulated TIMP-2 expression. Expressions of autophagy genes were upregulated by the cotinine treatment, whereas expressions of epithelial-to-mesenchymal transition markers were downregulated. In conclusion, our study, for the first time, demonstrated that cotinine, rather than nicotine, affects the properties of RPE cells in vitro, which could explain the smoking-induced RPE pathology.

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“…In addition, these experiments give rise to new opportunities for investigating the wide field of retina inflammation, aging, degeneration and repair by the help of an adequate culture system Klettner et al , 2012Miura et al 2010;Treumer et al 2012. In this coherence for example molecular regulation of vascular endothelial growth factor secretion and cell biological reactions after fucoidan application were investigated (Klettner et al 2013(Klettner et al , 2014Dithmer et al 2014).…”

Section: Maintenance Of Retinamentioning

confidence: 99%

Bridging the gap between traditional cell cultures and bioreactors applied in regenerative medicine: practical experiences with the MINUSHEET perfusion culture system

Minuth

Denk

2015

Cytotechnology

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To meet specific requirements of developing tissues urgently needed in tissue engineering, biomaterial research and drug toxicity testing, a versatile perfusion culture system was developed. First an individual biomaterial is selected and then mounted in a MINUSHEET Ò tissue carrier. After sterilization the assembly is transferred by fine forceps to a 24 well culture plate for seeding cells or mounting tissue on it. To support spatial (3D) development a carrier can be placed in various types of perfusion culture containers. In the basic version a constant flow of culture medium provides contained tissue with always fresh nutrition and respiratory gas. For example, epithelia can be transferred to a gradient container, where they are exposed to different fluids at the luminal and basal side. To observe development of tissue under the microscope, in a different type of container a transparent lid and base are integrated. Finally, stem/progenitor cells are incubated in a container filled by an artificial interstitium to support spatial development. In the past years the described system was applied in numerous own and external investigations. To present an actual overview of resulting experimental data, the present paper was written.

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Nicotine reduces VEGF-secretion and phagocytotic activity in porcine RPE

Abstract: Nicotine impedes RPE function (VEGF secretion, phagocytosis), which could be directly involved in the development of dry AMD and geographic atrophy.

Cited by 13 publications

References 39 publications

Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio

Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio

Disruption of retinal pigment epithelial cell properties under the exposure of cotinine

Bridging the gap between traditional cell cultures and bioreactors applied in regenerative medicine: practical experiences with the MINUSHEET perfusion culture system

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