Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma

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 toTek 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.
Source: eLife - Category: Biomedical Science Tags: Developmental Biology Human Biology and Medicine Source Type: research

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Abstract Glaucoma is a common heterogeneous eye disorder that may lead to irreversible blindness. In the present study, we examined whether etidronate, a member of bisphosphonates, may have neuroprotective effects in in vivo and in vitro rat model of glaucoma. In an in vivo setting, chronic ocular hypertension (COH) was induced in adult rat retina. We discovered that systemic injection of etidronate reduced COH-induced retinal oxidative stress, including caspase-3 activity and MDA level, as well as promoted retinal ganglion cell survival. In an in vitro setting, neonatal retinal ganglion cell was incubated with et...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions In conclusion, each of the MAPKs showed a specific spatio-temporal expression and activation pattern in the retina, ONH and optic nerve as a result of IOP elevation. These findings likely reflect the roles of the individual enzymes, and the cells in which they reside, in the developing pathology following IOP elevation. These data have implications for understanding the mechanisms of ocular pathology in diseases such as glaucoma.
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
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Source: Biomedical Beat Blog - National Institute of General Medical Sciences - Category: Research Authors: Tags: Cell Biology Cellular Imaging Cellular Processes Cool Images Source Type: blogs
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Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
Glaucoma, a leading cause of blindness worldwide, is a degenerative disease characterized by retinal ganglion cell (RGC) loss and optic nerve atrophy. Elevated intraocular pressure (IOP) is a main risk factor for onset and progression of the disease. Since increased IOP is the only modifiable risk factor, relevant models for glaucoma would comprise RGC and optic nerve damage triggered by ocular hypertension. Animal models of glaucoma have greatly contributed to the understanding of the molecular mechanisms of this pathology, and they have also facilitated the development of new pharmacological interventions. Although anima...
Source: Ophthalmic Research - Category: Opthalmology Source Type: research
In this study, a PET camera was used to examine individual differences in the D2 system in a group consisting of 181 healthy individuals between the age of 64 and 68. All participants also had to take part in an all-inclusive performance test of the long-term episodic memory, working memory and processing speed along with an MRI assessment (which was used to measure the size of various parts of the brain). Researchers could see that the D2 system was positively linked to episodic memory, but not to working memory or to processing speed by relating PET registrations to the cognitive data. Researchers could also see that the...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Glaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the opti...
Source: Journal of Neuroinflammation - Category: Neurology Authors: Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Abstract Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, and is the second leading cause of blindness worldwide. Elevated intraocular pressure is a well known risk factor for the development of glaucomatous optic neuropathy and pharmacological or surgical lowering of intraocular pressure represents a standard procedure in glaucoma treatment. However, the treatment options are limited and although lowering of intraocular pressure impedes disease progression, glaucoma cannot be cured by the currently available therapy concepts....
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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