Abstract
Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
