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Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma.
Thomson, Benjamin R; Carota, Isabel A; Souma, Tomokazu; Soman, Saily; Vestweber, Dietmar; Quaggin, Susan E.
Afiliación
  • Thomson BR; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States.
  • Carota IA; Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States.
  • Souma T; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States.
  • Soman S; Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States.
  • Vestweber D; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States.
  • Quaggin SE; Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States.
Elife ; 82019 10 17.
Article en En | MEDLINE | ID: mdl-31621585
ABSTRACT
Elevated intraocular pressure (IOP) due to insufficient aqueous humor outflow through the trabecular meshwork and Schlemm's canal (SC) is the most important risk factor for glaucoma, a leading cause of blindness worldwide. We previously reported loss of function mutations in the receptor tyrosine kinase TEK or its ligand ANGPT1 cause primary congenital glaucoma in humans and mice due to failure of SC development. Here, we describe a novel approach to enhance canal formation in these animals by deleting a single allele of the gene encoding the phosphatase PTPRB during development. Compared to Tek haploinsufficient mice, which exhibit elevated IOP and loss of retinal ganglion cells, Tek+/-;Ptprb+/- mice have elevated TEK phosphorylation, which allows normal SC development and prevents ocular hypertension and RGC loss. These studies provide evidence that PTPRB is an important regulator of TEK signaling in the aqueous humor outflow pathway and identify a new therapeutic target for treatment of glaucoma.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Ganglionares de la Retina / Glaucoma / Regulación del Desarrollo de la Expresión Génica / Receptor TIE-2 / Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Ganglionares de la Retina / Glaucoma / Regulación del Desarrollo de la Expresión Génica / Receptor TIE-2 / Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Año: 2019 Tipo del documento: Article