Choroidal Neovascular Membrane in Age-Related Macular Degeneration is Associated with Increased Interleukin-6

Yıldırım, Zühal; Uçgun, Nil İrem; Yildirim, Filiz; Sepici-Dinçel, Aylin

doi:10.1016/j.ijge.2012.01.018

Cited by 9 publications

(6 citation statements)

References 43 publications

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“…Inflammatory mediators, such as IL-1β, IL-6, IL-8, IL-10, IL-18, IL-12p70, TNFα, IFNγ, and MCP-1, play a vital role in the development of AMD and have angiogenic properties [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ], and their activity is upregulated following addition of LPS [ 36 ] or H 2 O 2 [ 35 ] to the media.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

et al. 2021

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Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total®; N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFNγ in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total® protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

et al. 2021

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“…IL-6 levels are increased in the serum of AMD patients when compared to healthy controls (Yildirim et al, 2012). An increased IL-6 level is associated with neovascularization, and it has been shown to increase VEGF expression in skeletal muscle myoblasts, human epidermoid carcinoma and glioma cells (Cohen et al, 1996).…”

Section: Inflammation In Amdmentioning

confidence: 99%

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells

Harju

2022

Acta Ophthalmologica

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Age‐related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide‐binding domain, leucine‐rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85–90%) and wet (10–15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti‐vascular endothelial growth factor (anti‐VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option.Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro‐oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone‐induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE‐19 cells). An age‐related eye disease study (AREDS) formulation (incl. omega‐3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone‐induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance.The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium‐derived factor (PEDF). Hydroquinone induced an NLRP3‐independent IL‐18 release and NLRP3 accumulation inside the IL‐1α‐primed cells. Resvega treatment reduced the extent of hydroquinone‐induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone‐ and impaired protein clearance‐induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.

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“…Subhi et al (2019) found that patients with neovascular AMD had higher levels of plasma IL‐6 compared to healthy controls, but that elevated plasma IL‐6 had little diagnostic value in discriminating from polypoidal choroidal vasculopathy which was not associated with differences in plasma IL‐6. Yildirim et al (2012) found that patients with neovascular AMD had significantly higher levels of serum IL‐6 compared to healthy controls.…”

Section: Resultsmentioning

confidence: 99%

“…The overall random‐effects SMD in systemic IL‐6 levels between patients with geographic atrophy and healthy controls was Glass’ Δ of 1.21 (95% CI: 0.41 to 2.01, p = 0.003), which indicates a very large effect size and a statistically significant difference. Twelve studies had eligible data for the subgroup analysis focused on patients with neovascular AMD (Yildirim et al 2012; Nassar et al 2014; Ambreen et al 2015; Haas et al 2015; Yildiz et al 2016; Čolak et al 2017; Budiene et al 2018; Spindler et al 2018; Agrawal et al 2019; Krogh Nielsen et al 2019; Subhi et al 2019). Here, we included a total of 1190 participants (577 patients with neovascular AMD and 613 controls).…”

Section: Resultsmentioning

confidence: 99%

Systemic levels of interleukin‐6 in patients with age‐related macular degeneration: a systematic review and meta‐analysis

Nahavandipour

Nielsen

Sørensen

et al. 2020

Acta Ophthalmologica

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Age-related macular degeneration (AMD) is the most prevalent cause of irreversible vision loss in industrialized countries. Several studies have investigated systemic interleukin-6 (IL-6) levels of patients with AMD. In this study, we systemically reviewed the literature to provide an overview of the field and used meta-analyses to provide a summary estimate of the standardized mean difference (SMD) of systemic IL-6 between patients with AMD and control individuals. We searched the literature databases PubMed/MEDLINE, Embase, Web of Science and the Cochrane Central on 1 June 2019 for relevant studies on humans. Two authors independently extracted data and evaluated risk of bias. We identified 19 studies for the qualitative review with a total of more than 3586 individuals (1865 controls and 1721 with AMD). We found an overall randomeffects SMD in systemic IL-6 levels 0.63 (95% CI: 0.28 to 0.99, p = 0.0005) corresponding to a medium effect size. In a subgroup analysis, we found that early AMD was not strongly associated with elevated IL-6 levels (0.12, 95% CI: À0.01 to 0.24, p = 0.06), which was in contrast to the significantly elevated IL-6 levels in patients with geographic atrophy (1.21, 95% CI: 0.41 to 2.01, p = 0.003) and patients with neovascular AMD (0.99, 95% CI: 0.34 to 1.63, p = 0.003). Our results show that the evidence today suggests an increased systemic IL-6 in patients with AMD, but that this may be a phenomenon more closely related to the late subtypes of AMD.

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Choroidal Neovascular Membrane in Age-Related Macular Degeneration is Associated with Increased Interleukin-6

Cited by 9 publications

References 43 publications

Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells

Systemic levels of interleukin‐6 in patients with age‐related macular degeneration: a systematic review and meta‐analysis

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