dc.contributor.author |
Mugisho, Odunayo O |
|
dc.contributor.author |
Aryal, Jyoti |
|
dc.contributor.author |
Shorne, Avik |
|
dc.contributor.author |
Lyon, Heather |
|
dc.contributor.author |
Acosta, Monica L |
|
dc.contributor.author |
Green, Colin R |
|
dc.contributor.author |
Rupenthal, Ilva D |
|
dc.coverage.spatial |
Switzerland |
|
dc.date.accessioned |
2023-10-05T01:59:29Z |
|
dc.date.available |
2023-10-05T01:59:29Z |
|
dc.date.issued |
2023-02 |
|
dc.identifier.citation |
(2023). International Journal of Molecular Sciences, 24(4), 3876-. |
|
dc.identifier.issn |
1422-0067 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/66133 |
|
dc.description.abstract |
Diabetic retinopathy (DR), a microvascular complication of diabetes, is associated with pronounced inflammation arising from the activation of a nucleotide-binding and oligomerization domain-like receptor (NLR) protein 3 (NLRP3) inflammasome. Cell culture models have shown that a connexin43 hemichannel blocker can prevent inflammasome activation in DR. The aim of this study was to evaluate the ocular safety and efficacy of tonabersat, an orally bioavailable connexin43 hemichannel blocker, to protect against DR signs in an inflammatory non-obese diabetic (NOD) DR mouse model. For retina safety studies, tonabersat was applied to retinal pigment epithelial (ARPE-19) cells or given orally to control NOD mice in the absence of any other stimuli. For efficacy studies, either tonabersat or a vehicle was given orally to the inflammatory NOD mouse model two hours before an intravitreal injection of pro-inflammatory cytokines, interleukin-1 beta, and tumour necrosis factor-alpha. Fundus and optical coherence tomography images were acquired at the baseline as well as at 2- and 7-day timepoints to assess microvascular abnormalities and sub-retinal fluid accumulation. Retinal inflammation and inflammasome activation were also assessed using immunohistochemistry. Tonabersat did not have any effect on ARPE-19 cells or control NOD mouse retinas in the absence of other stimuli. However, the tonabersat treatment in the inflammatory NOD mice significantly reduced macrovascular abnormalities, hyperreflective foci, sub-retinal fluid accumulation, vascular leak, inflammation, and inflammasome activation. These findings suggest that tonabersat may be a safe and effective treatment for DR. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
MDPI |
|
dc.relation.ispartofseries |
International journal of molecular sciences |
|
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.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Animals |
|
dc.subject |
Mice, Inbred NOD |
|
dc.subject |
Mice |
|
dc.subject |
Diabetic Retinopathy |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Inflammation |
|
dc.subject |
Benzamides |
|
dc.subject |
Connexin 43 |
|
dc.subject |
Administration, Oral |
|
dc.subject |
Inflammasomes |
|
dc.subject |
NLR Family, Pyrin Domain-Containing 3 Protein |
|
dc.subject |
inflammasome |
|
dc.subject |
retina |
|
dc.subject |
vascular breakdown |
|
dc.subject |
3101 Biochemistry and Cell Biology |
|
dc.subject |
31 Biological Sciences |
|
dc.subject |
3404 Medicinal and Biomolecular Chemistry |
|
dc.subject |
34 Chemical Sciences |
|
dc.subject |
3107 Microbiology |
|
dc.subject |
Eye Disease and Disorders of Vision |
|
dc.subject |
Diabetes |
|
dc.subject |
Neurosciences |
|
dc.subject |
5.1 Pharmaceuticals |
|
dc.subject |
5 Development of treatments and therapeutic interventions |
|
dc.subject |
Eye |
|
dc.subject |
Metabolic and endocrine |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Physical Sciences |
|
dc.subject |
Biochemistry & Molecular Biology |
|
dc.subject |
Chemistry, Multidisciplinary |
|
dc.subject |
Chemistry |
|
dc.subject |
VESICLE-ASSOCIATED PROTEIN |
|
dc.subject |
ANTIGEN PAL-E |
|
dc.subject |
NLRP3 INFLAMMASOME |
|
dc.subject |
DANGER SIGNAL |
|
dc.subject |
EXPRESSION |
|
dc.subject |
PATHWAY |
|
dc.subject |
VEGF |
|
dc.subject |
TARGET |
|
dc.subject |
0399 Other Chemical Sciences |
|
dc.subject |
0604 Genetics |
|
dc.subject |
0699 Other Biological Sciences |
|
dc.title |
Orally Delivered Connexin43 Hemichannel Blocker, Tonabersat, Inhibits Vascular Breakdown and Inflammasome Activation in a Mouse Model of Diabetic Retinopathy |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.3390/ijms24043876 |
|
pubs.issue |
4 |
|
pubs.begin-page |
3876 |
|
pubs.volume |
24 |
|
dc.date.updated |
2023-09-08T03:54:22Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
36835288 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/36835288 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
951593 |
|
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 |
1422-0067 |
|
dc.identifier.pii |
ijms24043876 |
|
pubs.number |
ARTN 3876 |
|
pubs.record-created-at-source-date |
2023-09-08 |
|
pubs.online-publication-date |
2023-02-15 |
|