4.7 Article

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

Journal

Publisher

MDPI
DOI: 10.3390/ijms22010298

Keywords

connexin43; hemichannels; inflammation; inflammasome; diabetic retinopathy; tonabersat

Funding

  1. Maurice and Phyllis Paykel Trust
  2. Auckland Medical Research Foundation [1117015]
  3. W&B Chair in Ophthalmology
  4. Buchanan Charitable Foundation

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available