Tonabersat Inhibits Connexin43 Hemichannel Opening and Inflammasome Activation in an In Vitro Retinal Epithelial Cell Model of Diabetic Retinopathy.

Int J Mol Sci

Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.

Published: December 2020

This study was undertaken to evaluate the connexin hemichannel blocker tonabersat for the inhibition of inflammasome activation and use as a potential treatment for diabetic retinopathy. Human retinal pigment epithelial cells (ARPE-19) were stimulated with hyperglycemia and the inflammatory cytokines IL-1β and TNFα in order to mimic diabetic retinopathy molecular signs in vitro. Immunohistochemistry was used to evaluate the effect of tonabersat treatment on NLRP3, NLRP1, and cleaved caspase-1 expression and distribution. A Luminex cytokine release assay was performed to determine whether tonabersat affected proinflammatory cytokine release. NLRP1 was not activated in ARPE-19 cells, and IL-18 was not produced under disease conditions. However, NLRP3 and cleaved caspase-1 complex formation increased with hyperglycemia and cytokine challenge but was inhibited by tonabersat treatment. It also prevented the release of proinflammatory cytokines IL-1β, VEGF, and IL-6. Tonabersat therefore has the potential to reduce inflammasome-mediated inflammation in diabetic retinopathy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794685PMC
http://dx.doi.org/10.3390/ijms22010298DOI Listing

Publication Analysis

Top Keywords

diabetic retinopathy
16
inflammasome activation
8
cytokines il-1β
8
tonabersat treatment
8
cleaved caspase-1
8
cytokine release
8
tonabersat
6
tonabersat inhibits
4
inhibits connexin43
4
connexin43 hemichannel
4

Similar Publications

Objective: This study aims to examine the reduction and subsequent recovery of routine digital screening (RDS) uptake in England from 2018 to 2022, exploring national, regional and individual Diabetic Eye Screening Programme (DESP) levels. The COVID-19 lockdown in most areas of England was from 26 March 2020 to 23 June 2020 (first national lockdown), 5 November 2020 to 2 December 2020 (second national lockdown) and 6 January 2021 to 8 March 2021 (third national lockdown).

Design: Retrospective data analysis.

View Article and Find Full Text PDF

Prevalence of microvascular complications and associated factors among diabetes mellitus patients in Ethiopia: A systematic review and Meta-analysis.

Microvasc Res

December 2024

Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia; Research Center for Tuberculosis and Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Prinshof, 0084 Pretoria, South Africa.

Background: Diabetes mellitus (DM) is a metabolic abnormality affecting 537 million people worldwide. Poor glycemic control, longer duration, and poor medication adherence increased the risk of DM complications. Comprehensive evidence on the pooled prevalence of microvascular complications in DM patients in Ethiopia is not available.

View Article and Find Full Text PDF

Ginsenoside Ro prevents endothelial injury via promoting Epac1/AMPK- mediated mitochondria protection in early diabetic retinopathy.

Pharmacol Res

December 2024

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education. Electronic address:

Diabetic retinopathy (DR) is a blinding complication of microangiopathy. First-line therapeutic drugs are all focused on late-stage DR and have several side effects, which could not meet clinical needs. The plant-derived ginsenoside Ro (Ro) has a variety of effective anti-inflammatory, immune-regulating, and cardiovascular protective effects, but its microvascular protective effects are rarely studied.

View Article and Find Full Text PDF

This article reviews the critical issue of diabetic retinopathy (DR) in pregnant women with diabetes mellitus (DM), and describes the current understanding of the features of DM progression during pregnancy, as well as its pathogenic mechanisms, risk factors, and preventive measures for manifestation and progression of DR during gestation.

View Article and Find Full Text PDF

The introduction of faricimab, a drug targeting both vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2, has enabled the implementation of the highly effective dual inhibition strategy in real clinical practice for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), both previously treated with intravitreal injections and newly diagnosed. This article presents a series of 11 clinical cases involving patients with nAMD and DME who received loading doses of faricimab and continued ophthalmological observation. Among them, three patients with nAMD and two with DME were treatment-naïve, while the others were switched from alternative therapies to faricimab.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!