{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:27Z","timestamp":1787828307578,"version":"build-2784847793"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Zealand Lottery Health Research","award":["22385"],"award-info":[{"award-number":["22385"]}]},{"name":"Auckland Uniservices Ltd","award":["5000293"],"award-info":[{"award-number":["5000293"]}]},{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"publisher","award":["3708721"],"award-info":[{"award-number":["3708721"]}],"id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001527","name":"New Zealand Optometric Vision Research Foundation","doi-asserted-by":"publisher","award":["CC51352"],"award-info":[{"award-number":["CC51352"]}],"id":[{"id":"10.13039\/501100001527","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.<\/jats:p>","DOI":"10.3390\/ijms22041755","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:49:26Z","timestamp":1613090966000},"page":"1755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases"],"prefix":"10.3390","volume":"22","author":[{"given":"Mohd N.","family":"Mat Nor","sequence":"first","affiliation":[{"name":"School of Optometry and Vision Science, University of Auckland, Auckland 1142, New Zealand"},{"name":"Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-5994","authenticated-orcid":false,"given":"Ilva D.","family":"Rupenthal","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology and New Zealand National Eye Centre, University of Auckland, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3459-6298","authenticated-orcid":false,"given":"Colin R.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and New Zealand National Eye Centre, University of Auckland, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-339X","authenticated-orcid":false,"given":"Monica L.","family":"Acosta","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, New Zealand National Eye Centre, Centre for Brain Research, Brain Research New Zealand\u2014Rangahau Roro Aotearoa, University of Auckland, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000316942","article-title":"Connexin channel-dependent signaling pathways in inflammation","volume":"48","author":"Scheckenbach","year":"2011","journal-title":"J. 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