dc.contributor.author |
Mat Nor, Mohd Nasir |
|
dc.contributor.author |
Rupenthal, Ilva D |
|
dc.contributor.author |
Green, Colin R |
|
dc.contributor.author |
Acosta, Monica L |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2023-10-06T01:44:37Z |
|
dc.date.available |
2023-10-06T01:44:37Z |
|
dc.date.issued |
2020-01 |
|
dc.identifier.citation |
(2020). Neurotherapeutics, 17(1), 371-387. |
|
dc.identifier.issn |
1933-7213 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/66179 |
|
dc.description.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 3 months 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 2 weeks. 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. |
|
dc.format.medium |
Print |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
Astrocytes |
|
dc.subject |
Microglia |
|
dc.subject |
Retina |
|
dc.subject |
Animals |
|
dc.subject |
Rats, Sprague-Dawley |
|
dc.subject |
Retinal Diseases |
|
dc.subject |
Retinitis |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Benzamides |
|
dc.subject |
Benzopyrans |
|
dc.subject |
Connexins |
|
dc.subject |
Connexin 43 |
|
dc.subject |
Administration, Oral |
|
dc.subject |
Female |
|
dc.subject |
Male |
|
dc.subject |
Connexin43 |
|
dc.subject |
Macular degeneration |
|
dc.subject |
choroid |
|
dc.subject |
diabetic retinopathy |
|
dc.subject |
inflammasome |
|
dc.subject |
inflammation |
|
dc.subject |
tonabersat |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
3212 Ophthalmology and Optometry |
|
dc.subject |
Eye Disease and Disorders of Vision |
|
dc.subject |
Neurosciences |
|
dc.subject |
Aging |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
2 Aetiology |
|
dc.subject |
Eye |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Clinical Neurology |
|
dc.subject |
Pharmacology & Pharmacy |
|
dc.subject |
Neurosciences & Neurology |
|
dc.subject |
GAP-JUNCTION MODULATOR |
|
dc.subject |
MIMETIC PEPTIDE |
|
dc.subject |
NLRP3 INFLAMMASOME |
|
dc.subject |
SPINAL-CORD |
|
dc.subject |
CX43 HEMICHANNELS |
|
dc.subject |
DOUBLE-BLIND |
|
dc.subject |
MOUSE MODEL |
|
dc.subject |
CELL-DEATH |
|
dc.subject |
MIGRAINE |
|
dc.subject |
INJURY |
|
dc.subject |
1113 Opthalmology and Optometry |
|
dc.subject |
Biomedical |
|
dc.subject |
Clinical Medicine and Science |
|
dc.subject |
1109 Neurosciences |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.subject |
1117 Public Health and Health Services |
|
dc.subject |
3209 Neurosciences |
|
dc.subject |
3214 Pharmacology and pharmaceutical sciences |
|
dc.subject |
5202 Biological psychology |
|
dc.title |
Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1007/s13311-019-00786-5 |
|
pubs.issue |
1 |
|
pubs.begin-page |
371 |
|
pubs.volume |
17 |
|
dc.date.updated |
2023-09-08T04:00:17Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
31637594 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/31637594 |
|
pubs.end-page |
387 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RetrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
784822 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
School of Medicine |
|
pubs.org-id |
Ophthalmology Department |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
pubs.org-id |
Optometry and Vision Science |
|
dc.identifier.eissn |
1878-7479 |
|
dc.identifier.pii |
10.1007/s13311-019-00786-5 |
|
pubs.record-created-at-source-date |
2023-09-08 |
|
pubs.online-publication-date |
2019-10-21 |
|