Abstract

Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative to conventional cigarettes (C-cigarette), electronic cigarettes (E-cigarette) have been globally promoted and are currently widely used. The increasing usage of E-cigarettes raises concerns with regard to short- (2 weeks), medium- (3 months), and long- (8 months) term consequences related to retinal tissue. In this report, a controlled study in mouse models was conducted to probe the comprehensive effects of E-cigarette vapor on retina, retinal pigmented epithelium (RPE), and choroidal tissues by (1) comparing the effects of C-cigarette smoke and E-cigarette vapor on retina separately and (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory (IL-1β, TNFα, iNOS) and angiogenic (VEGF, PEDF) mediators in retina/RPE/choroid by ELISA assays. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid as compared to retinal tissue, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might also be related to the onset of wet AMD in humans.Key messagesC-cigarette smoke exposure promotes an inflammatory reaction in the retina in vivo.Mice exposed to E-cigarette (nicotine-free) vapor develop inflammatory and angiogenic reactions more pronounced in RPE and choroid compared to retinal tissue, while nicotine-containing E-cigarette vapor causes even a more serious reaction.Both inflammatory and pro-angiogenic reactions increase with the extension of E-cigarette vapor exposure time.

Highlights

  • Age-related macular degeneration (AMD) is one of the leading causes of severe vision impairment among the global population [1]

  • In wet AMD, it probably starts with the dysfunction/loss of choroidal vasculature alone or with retinal pigmented epithelium (RPE) layer together, followed by the accumulation of proinflammatory mediators in choriocapillaris, and the subsequent production of excessive angiogenic substances by RPE because of hypoxia, which will result in angiogenesis from the choroidal vessels into the retina (CNV), and photoreceptor loss [28, 29]

  • The comprehensive results from retina, RPE and choroid after medium-term exposure to E-cigarette vapor revealed that both nicotine-containing and nicotine-free E-cigarette vapor could stimulate the expression of pro-inflammatory and angiogenic mediators and accumulate in the RPE and choroidal tissues

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Summary

Introduction

Age-related macular degeneration (AMD) is one of the leading causes of severe vision impairment among the global population [1]. Previous studies have demonstrated that pro-inflammatory cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) can promote angiogenesis in choroidal neovascular membranes [3, 4], and are able to disrupt the structure and function of the outer and inner blood-retinal barrier (BRB) [5,6,7], leading to the progression of wet AMD. Pigment epithelium-derived factor (PEDF) is an anti-angiogenic and neuroprotective factor It affects the proliferation and the oxidative stress state of choroidal endothelial cells [10]. Animal studies showed that nicotine-containing E-cigarette vapor exposure could increase the pulmonary inflammation and oxidative stress in mice [21, 22]. The effect of E-cigarette vapor on RPE and choroid was determined and the changes with regard to inflammatory and angiogenic mediators in retina/RPE/choroid were analyzed in order to evaluate a potential relationship between E-cigarette vapor exposure and the induction of inflammatory angiogenic effects in mice, which might be related to the onset of wet AMD in humans

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