Mostrar el registro sencillo del ítem
dc.contributor.author
Galan, Alba
dc.contributor.author
Barcelona, Pablo Federico
dc.contributor.author
Nedev, Hinyu
dc.contributor.author
Sarunic, Marinko V.
dc.contributor.author
Jian, Yifan
dc.contributor.author
Saragovi, H. Uri
dc.date.available
2018-06-14T15:36:19Z
dc.date.issued
2017-06
dc.identifier.citation
Galan, Alba; Barcelona, Pablo Federico; Nedev, Hinyu; Sarunic, Marinko V.; Jian, Yifan; et al.; Subconjunctival delivery of p75NTR antagonists reduces the inflammatory, vascular, and neurodegenerative pathologies of diabetic retinopathy; Association for Research in Vision and Ophthalmology; Investigative Ophthalmology & Visual Science; 58; 7; 6-2017; 2852-2862
dc.identifier.issn
0146-0404
dc.identifier.uri
http://hdl.handle.net/11336/48639
dc.description.abstract
The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. METHODS. We compared the pharmacokinetics of a single 40 lg subconjunctival (SCJ) depot to the reported effective 5 lg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. RESULTS. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. CONCLUSIONS. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Association for Research in Vision and Ophthalmology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Antagonist
dc.subject
Diabetic Retinopathy
dc.subject
P75 Receptor
dc.subject
Subconjunctival
dc.subject
Target
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Subconjunctival delivery of p75NTR antagonists reduces the inflammatory, vascular, and neurodegenerative pathologies of diabetic retinopathy
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-11T12:58:31Z
dc.identifier.eissn
1552-5783
dc.journal.volume
58
dc.journal.number
7
dc.journal.pagination
2852-2862
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Rockville
dc.description.fil
Fil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; Canadá
dc.description.fil
Fil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Nedev, Hinyu. Mc Gill University. Lady Davis Research Intitute; Canadá
dc.description.fil
Fil: Sarunic, Marinko V.. University Fraser Simon; Canadá
dc.description.fil
Fil: Jian, Yifan. University Fraser Simon; Canadá
dc.description.fil
Fil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canadá
dc.journal.title
Investigative Ophthalmology & Visual Science
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/28570737
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1167/iovs.16-20988
Archivos asociados