Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma
- Northwestern University, United States
- Max Planck Institute for Molecular Biomedicine, Germany
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.
Data availability
All data described have been included in the manuscript. No data sets were generated during the course of this study.
Article and author information
Author details
Benjamin R Thomson
Funding
National Institutes of Health (R01 HL124120)
- Susan E Quaggin
National Institutes of Health (R01 EY025799)
- Susan E Quaggin
National Institutes of Health (P30 DK114857)
- Susan E Quaggin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the ARVO guidelines for care and use of vertebrate research subjects in eye research. All animal experiments were approved by the Animal Care Committee at the Center for Comparative Medicine of Northwestern University (Evanston, Illinois, USA) under animal protocols IS00002777, IS00006571 and IS00003091.
Copyright
© 2019, Thomson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma
eLife 8:e48474.
https://doi.org/10.7554/eLife.48474
