scholarly journals Curcumin Modulates DNA Methyltransferase Functions in a Cellular Model of Diabetic Retinopathy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Andrea Maugeri ◽  
Maria Grazia Mazzone ◽  
Francesco Giuliano ◽  
Manlio Vinciguerra ◽  
Guido Basile ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Dna Methyltransferase ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Public Health Issue ◽  
Ros Production ◽  
Cellular Model ◽  
Early Effect

Hyperglycaemia-induced oxidative stress appears to be involved in the aetiology of diabetic retinopathy (DR), a major public health issue, via altering DNA methylation process. We investigated the effect of hyperglycaemia on retinal DNA methyltransferase (DNMT) expression in diabetic mice, using Gene Expression Omnibus datasets. We also evaluated the effect of curcumin both on high glucose-induced reactive oxygen species (ROS) production and altered DNMT functions, in a cellular model of DR. We observed that three months of hyperglycaemia, in insulin-deficient Ins2Akita mice, decrease DNMT1 and DNMT3a expression levels. In retinal pigment epithelium (RPE) cells, we also demonstrated that high glucose-induced ROS production precedes upregulation of DNMT expression and activity, suggesting that changes in DNMT function could be mediated by oxidative stress via a potential dual effect. The early effect results in decreased DNMT activity, accompanied by the highest ROS production, while long-term oxidative stress increases DNMT activity and DNMT1 expression. Interestingly, treatment with 25 μM curcumin for 6 hours restores ROS production, as well as DNMT functions, altered by the exposure of RPE to acute and chronic high glucose concentration. Our study suggests that curcumin may represent an effective antioxidant compound against DR, via restoring oxidative stress and DNMT functions, though further studies are recommended.

scholarly journals Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy

PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0228895 ◽  
Author(s):  
María Constanza Potilinski ◽  
Gustavo A. Ortíz ◽  
Juan P. Salica ◽  
Emiliano S. López ◽  
Mariano Fernández Acquier ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Retinal Pigment Epithelium ◽  
Mechanism Of Action ◽  
High Glucose ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelium Cells ◽  
Alpha 1 Antitrypsin ◽  
Epithelium Cells ◽  
Potential Use

Circ_0000615 promotes high glucose-induced human retinal pigment epithelium cell apoptosis, inflammation and oxidative stress via miR-646/YAP1 axis in diabetic retinopathy

2021 ◽  
pp. 112067212110202
Author(s):  
Qiang Zeng ◽  
YiTing Luo ◽  
Junxu Fang ◽  
Shuang Xu ◽  
Yuan-Hua Hu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Retinal Pigment Epithelium ◽  
Western Blot ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ros Generation ◽  
Human Retinal Pigment Epithelium ◽  
Cell Dysfunction

Background: Diabetic retinopathy (DR), a common complication of diabetes mellitus, is the major cause of visual impairment and blindness. Circ_0000615 was found to be elevated in retina samples of diabetic patients. Hence, the detailed effects and molecular mechanisms of circ_0000615 in DN progression were explored. Methods: The levels of circ_0000615, microRNA (miR)-646 and YAP1 (yes-associated protein 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, inflammation and reactive oxygen species (ROS) generation were determined using cell counting kit-8 assay, flow cytometry, caspase3 activity analysis, Western blot, enzyme-linked immunosorbent assay (ELISA) and Dichlorofluorescein diacetate (DCFH-DA) assay, respectively. The binding interaction between miR-646 and circ_0000615 or YAP1 was determined using dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Results: Circ_0000615 was elevated in high glucose (HG)-induced human retinal pigment epithelium (HRPE) cells. Knockdown of circ_0000615 attenuated HG-triggered HRPE cell apoptosis, inflammation, and ROS generation. Mechanistically, miR-646 was confirmed to be a target of circ_0000615, inhibition of miR-646 reversed the protective effects of circ_0000615 knockdown on HG-evoked HRPE cell dysfunction. MiR-646 was verified to target YAP1, overexpression of YAP1 abolished the impairment induced by miR-646 on HG-induced HRPE cell damage. Besides that, we confirmed that circ_0000615 could regulate YAP1 expression via miR-646. Conclusion: Circ_0000615 contributed to HG-induced HRPE cell dysfunction via miR-646/YAP1 axis, suggesting a novel insight into the pathogenesis of DR and a potential candidate for DR treatment.

scholarly journals Casein Kinase 2-Interacting Protein-1 Alleviates High Glucose-Reduced Autophagy, Oxidative Stress, and Apoptosis in Retinal Pigment Epithelial Cells via Activating the p62/KEAP1/NRF2 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xia Zhao ◽  
Jing Wang ◽  
Pei Li ◽  
Liying Tang ◽  
Yuzhi Bai
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Interacting Protein ◽  
Rpe Cells ◽  
Pigment Epithelial

Background. Casein kinase 2-interacting protein-1 (CKIP-1) has been proved to be associated with complications of diabetes. Diabetic retinopathy is a main diabetic complication which usually leads to blindness. The current study aims to investigate the role of CKIP-1 in high glucose-treated retinal pigment epithelial (RPE) cells which is a component of blood-retinal barriers. Methods. The RPE cells, ARPE-19, are treated with high glucose to mimic the diabetic stimulation. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively. Results. CKIP-1 was expressed at a lower level in high glucose-treated cells than in normal glucose cells. Overexpression of CKIP-1 enhanced the Nrf2 translocation to the nucleus. Furthermore, high glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. Also, CKIP-1 regulates the p62/Keap1/Nrf2 signaling, which might be the potential mechanism in this model. Conclusion. In conclusion, CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

Sign in / Sign up

Export Citation Format

Share Document