A Novel Mouse Model of TGFβ2-Induced Ocular Hypertension Using Lentiviral Gene Delivery.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
21 Jun 2022
Historique:
received: 17 04 2022
revised: 13 06 2022
accepted: 17 06 2022
entrez: 9 7 2022
pubmed: 10 7 2022
medline: 14 7 2022
Statut: epublish

Résumé

Glaucoma is a multifactorial disease leading to irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form and is associated with the elevation of intraocular pressure (IOP). Reduced aqueous humor (AH) outflow due to trabecular meshwork (TM) dysfunction is responsible for IOP elevation in POAG. Extracellular matrix (ECM) accumulation, actin cytoskeletal reorganization, and stiffening of the TM are associated with increased outflow resistance. Transforming growth factor (TGF) β2, a profibrotic cytokine, is known to play an important role in the development of ocular hypertension (OHT) in POAG. An appropriate mouse model is critical in understanding the underlying molecular mechanism of TGFβ2-induced OHT. To achieve this, TM can be targeted with recombinant viral vectors to express a gene of interest. Lentiviruses (LV) are known for their tropism towards TM with stable transgene expression and low immunogenicity. We, therefore, developed a novel mouse model of IOP elevation using LV gene transfer of active human TGFβ2 in the TM. We developed an LV vector-encoding active hTGFβ2

Identifiants

pubmed: 35805889
pii: ijms23136883
doi: 10.3390/ijms23136883
pmc: PMC9266301
pii:
doi:

Substances chimiques

Actins 0
Transforming Growth Factor beta2 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NEI NIH HHS
ID : R01 EY026177
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY028616
Pays : United States
Organisme : NIH HHS
ID : EY022077 (G.S.Z.), EY028616 (G.S.Z.), and EY026177 (G.S.Z.)
Pays : United States

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Auteurs

Shruti V Patil (SV)

Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Ramesh B Kasetti (RB)

Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

J Cameron Millar (JC)

Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Gulab S Zode (GS)

Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

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