A5079808447- Glaucoma and retinal disorders
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Corneal surgery and disorders
- Nerve injury and regeneration
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
- Retinal and Macular Surgery
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Fibroblast Growth Factor Research
- Neural dynamics and brain function
- Cerebral Venous Sinus Thrombosis
- Kruppel-like factors research
- Mitochondrial Function and Pathology
- TGF-β signaling in diseases
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Biomarkers in Disease Mechanisms
- S100 Proteins and Annexins
- Nuclear Receptors and Signaling
- Ocular Oncology and Treatments
- Cancer-related molecular mechanisms research
- Retinal Imaging and Analysis
- Liver Diseases and Immunity
Stanford University
2019-2025
Vision Eye Institute
2024
University of North Texas Health Science Center
2014-2021
University of North Texas
2014-2021
Wellcome/MRC Institute of Metabolic Science
2020
Addenbrooke's Hospital
2020
Wellcome Trust
2020
Stanford Medicine
2019
Smith-Kettlewell Eye Research Institute
2015-2018
Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in AH and TM primary open angle glaucoma (POAG) patients induces POAG-associated changes, CLANs. We determined role individual TGFβ2 signaling pathways CLAN formation.Cultured nonglaucomatous human (NTM) cells were treated with control...
Understanding the molecular mechanism of glaucoma and development neuroprotectants is significantly hindered by lack a reliable animal model that accurately recapitulates human glaucoma. Here, we sought to develop mouse for secondary often observed in humans after silicone oil (SO) blocks pupil or migrates into anterior chamber following vitreoretinal surgery. We significant intraocular pressure (IOP) elevation intracameral injection SO, SO removal allows IOP return quickly normal. This...
Optic neuropathies are a group of optic nerve (ON) diseases caused by various insults including glaucoma, inflammation, ischemia, trauma, and genetic deficits, which characterized retinal ganglion cell (RGC) death ON degeneration. An increasing number genes involved in RGC intrinsic signaling have been found to be promising neural repair targets that can potentially modulated directly gene therapy, if we achieve specific targeting. To address this challenge, first used adeno-associated virus...
Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, the molecular mechanisms underlying neurodegeneration unknown. We find that OPTN C-terminus truncation (OPTN∆C) causes late-onset of retinal ganglion cells (RGCs), optic nerve (ON), spinal cord motor neurons, preceded by decrease axonal mitochondria in mice. discover directly interacts with both microtubules mitochondrial transport complex...
Purpose: Wnt/β-catenin signaling in the trabecular meshwork (TM) is required for maintaining normal intraocular pressure (IOP), although mechanism(s) behind this are unknown. We hypothesize that regulates IOP via β-catenin's effects on cadherin junctions. Methods: Nonglaucomatous primary human TM (NTM) cells were treated with or without 100 ng/ml Wnt3a, 1 μg/ml sFRP1, both 4 to 48 hours. Cells immunostained β-catenin, total cadherins, isoforms. Membrane proteins whole-cell lysates isolated...
Abstract Recently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here characterize two additional variations of this that simulate distinct glaucoma types. The first is a chronic produced by high frequency (HF) pupillary dilation after SO-induced block, which shows sustained moderate IOP elevation and corresponding slow, mild We also demonstrate although SO removal quickly returns to normal, the neurodegeneration...
Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe novel, effective method consistently inducing stable IOP elevation in mice that mimics the post-operative complication of using silicone oil (SO) as tamponade agent human vitreoretinal surgery. In this protocol, SO injected into anterior chamber mouse eye to block pupil and prevent inflow aqueous humor. The posterior accumulates humor turn increases segment. A single injection produces...
The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced hypertension (OHT) and glaucoma (GIG). OHT occurs in about 40% the general population, while other 60% are resistant. This study aims to determine genes pathways involved differential GC responsiveness trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), fellow used establish a TM (BTM) cell strain. Based on maximum IOP change perfused eye, BTM strain...
Purpose: Elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) results from glaucomatous damage to the trabecular meshwork (TM). The glaucoma-associated factor TGFβ2 is increased aqueous humor and TM of POAG patients. We hypothesize that histone acetylation has a role dysregulated expression. Methods: Protein was compared between nonglaucomatous (NTM) (GTM) cells using Western immunoblotting (WB). Nonglaucomatous were treated with 10 nM thailandepsin-A (TDP-A), potent...
bleeding rather tend to confirm, and yet, as in the first case, although Dr. A. Ptrkin W. E. Hume at necropsy examined interior of chest carefully, no sign injury was apparent either on surface lung or intercostal artery.As haemorrhage always occurred patients who-e temperature high it may be that a poisoned state blood is responsible for bleeding, alone combined with alteration pressure.The blood-vessels would become unhealthy if injured probably not contract so well.They might rupture...
Abstract Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, the molecular mechanisms underlying neurodegeneration unknown. We found that OPTN C-terminus truncation (OPTNΔC) causes late-onset of retinal ganglion cells (RGCs), optic nerve (ON), spinal cord motor neurons, preceded by striking decrease axonal mitochondria. Surprisingly, we discover directly interacts with both microtubules...
Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe novel, effective method consistently inducing stable IOP elevation in mice that mimics the post-operative complication of using silicone oil (SO) as tamponade agent human vitreoretinal surgery. In this protocol, SO injected into anterior chamber mouse eye to block pupil and prevent inflow aqueous humor. The posterior accumulates humor turn increases segment. A single injection produces...
Background: The primary risk factor for primary-open angle glaucoma (POAG) is increased intraocular pressure (IOP). In POAG patients, the outflow resistance through trabecular meshwork (TM) abnormally elevated. One of important glaucoma-associated pathological changes in TM formation excessive cross-linked actin networks (CLANs). CLANs are web-like polygonal structures found confluent cells and tissues. Glaucoma-associated factors transforming forming growth beta 2 (TGFβ2) glucocorticoids...
Loss-of-function mutations in both alleles of the human insulin receptor gene (INSR) cause extreme resistance (IR) and usually death childhood, with few effective therapeutic options. Bivalent antireceptor antibodies can elicit insulin-like signaling by mutant INSR cultured cells, but whether this translates into meaningful metabolic benefits vivo, wherein dynamics recycling are more complex, is unknown. To address this, we adopted a strategy to model receptoropathy mice, using Cre...
Abstract Understanding the molecular mechanism of glaucoma and development neuroprotectants are significantly hindered by lack a reliable animal model that accurately recapitulates human glaucoma. Here we sought to develop mouse for secondary is often observed in humans after silicone oil (SO) blocks pupil or migrates into anterior chamber following vitreoretinal surgery. We similar intraocular pressure (IOP) elevation intracameral injection eyes SO, removing SO allows IOP level quickly...