Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms22010298
Keywords
connexin43; hemichannels; inflammation; inflammasome; diabetic retinopathy; tonabersat
Funding
- Maurice and Phyllis Paykel Trust
- Auckland Medical Research Foundation [1117015]
- W&B Chair in Ophthalmology
- Buchanan Charitable Foundation
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The study demonstrated that tonabersat can inhibit inflammasome activation and proinflammatory cytokine release in diabetic retinopathy, showing potential for reducing inflammation in this condition.
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-1 beta and TNF alpha 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-1 beta, VEGF, and IL-6. Tonabersat therefore has the potential to reduce inflammasome-mediated inflammation in diabetic retinopathy.
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