A5088589203- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurological Disorders and Treatments
- Diet and metabolism studies
- Biochemical effects in animals
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Spinal Cord Injury Research
- Retinopathy of Prematurity Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Nerve injury and regeneration
- Calpain Protease Function and Regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Adipose Tissue and Metabolism
- Amino Acid Enzymes and Metabolism
- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Biochemical Acid Research Studies
- NF-κB Signaling Pathways
- Nitric Oxide and Endothelin Effects
University of North Texas
2021-2025
University of North Texas Health Science Center
2021-2025
Smith-Kettlewell Eye Research Institute
2024
Northeast Ohio Medical University
2012-2021
University of Washington
2003-2013
Neurological Surgery
2003-2010
University of Washington Medical Center
2009
Seattle University
2009
University of California, San Francisco
2003
University of California, Irvine
2003
Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a progressive loss of vision. Previous studies suggest RGC death responsible for vision in glaucoma, yet evidence from other neurodegenerative diseases suggests axonal degeneration, the absence neuronal loss, can significantly affect function. To characterize degeneration DBA/2 mouse model we quantified RGCs mice various ages using neuronal-specific nuclear protein (NeuN) immunolabeling, retrograde labeling, optic nerve...
An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the retinal ganglion cell (RGC) neurons their axons in optic nerve. Here we show that, like other neurodegenerations, injury appears mouse glaucoma. Where RGC terminate superior colliculus, reduction active follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to deficits increases with age not necessarily associated elevated ocular pressure....
purpose. In the context of retinal ganglion cell (RGC) axon degeneration in optic nerve that occurs glaucoma, microglia become activated, then phagocytic, and redistribute head. The authors investigated potential contribution activation to glaucoma progression DBA/2J chronic mouse model. methods. treated 6-week-old mice for 25 weeks with minocycline, a tetracycline derivative known reduce improve neuronal survival other models neurodegenerative disease. They quantified RGC numbers...
Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that γ-synuclein (Sncg) mRNA expressed specifically and highly adult mouse RGCs, we show DBA/2J model glaucoma there not only a loss expressing this gene, but also downregulation gene expression Sncg many other genes large numbers RGCs. This RGCs occurs together with reductions FluoroGold (FG) retrograde transport. Surprisingly, are...
Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using microbead injection technique to chronically raise IOP 15 or 30 d in mice, we identified the early changes visual response properties of different types retinal ganglion cells (RGCs) and correlated these with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well In such eyes, multielectrode array recordings revealed that four RGC show diverse alterations...
The DBA/2J mouse is a model for secondary angle-closure glaucoma, due to iris atrophy and pigment dispersion, which ultimately lead increased intraocular pressure (IOP). study was undertaken correlate changes in retinal gene expression with IOP elevation by performing microarray analysis of RNA from mice at 3 months before disease onset 8 after elevation.IOP monitored monthly animals, animals normal (3 months) or elevated (8 were identified. prepared three individual retinas each age, the...
Abstract In many CNS diseases, proliferation becomes dysregulated; cells divide and participate in pathological processes. Gliosis is a fundamental response to trauma or disease which cell hypertrophy play prominent roles. The DBA/2J mouse glaucoma model mice experience gliosis concomitant with raised intraocular pressure that leads slow progressive retinal ganglion axonopathy. We sought determine if glaucomatous changes DBA/2 retina would alter the regulation of proliferation, specifically...
Author(s): Tezel, Gulgun; Fourth ARVO/Pfizer Ophthalmics Research Institute Conference Working Group
We tested the hypothesis that glaucoma disrupts electrophysiological conduction properties and axon function in optic nerve as a of intraocular pressure (IOP) levels age DBA/2J mouse model glaucoma. The amplitude integral electrical signals evoked along axons decreased considerably by 6 months increasing IOP levels. At young ages, raised was directly associated with increased vulnerability to metabolic challenge. Changes physiological nerves were accentuated aging, leading loss compound...
Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, mechanisms leading to onset progression remain unknown. Molecular analysis various glaucoma models has revealed involvement non-neuronal cell populations, including astrocytes, Mueller glia microglia, at early stages glaucoma. High-dose irradiation was reported have significant long-term protective...
Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense long-term testing, few studies have modeled antioxidant therapy for prevention neurodegeneration. We investigated contribution oxidative pathogenesis glaucoma DBA/2J mouse model Similar other we observed lipid peroxidation upregulation stress-related mRNA protein retina. To test role disease progression, chose deliver naturally occurring,...
Glaucoma is a chronic degenerative disease for which inflammation considered to play pivotal role in the pathogenesis and progression. In this study, we examined impact of ketogenic diet on evident glaucoma as follow-up recent set experiments determined that protected retinal ganglion cell structure function. Both sexes DBA/2J (D2) mice were placed (keto) or standard rodent chow (untreated) 8 weeks beginning at 9 months age. DBA/2J-Gpnmb+ (D2G) also used non-pathological genetic control D2...
Decreased ATP correlates with intraocular pressure exposure in the optic nerves of mice glaucoma. To understand what underlies this energy deficit, we examined mitochondria myelinated nerve axons DBA/2J mouse, a model glaucoma secondary to iris pigment disease, and DBA/2(wt-gpnmb) control strain.Mitochondrial length, width, surface area, health status were measured 30 electron microscopic fields within portion from at 3, 6, 10 months age. Protein was isolated for analysis PINK1, Parkin,...
To investigate quantitatively the relationships between elevated intraocular pressure (IOP), axonal loss, and corneal thickness in DBA/2 mouse model of glaucoma, to understand better how these factors contribute disease progression.IOP was measured with a handheld tonometer (Tono-Pen; Medtronic Solan, Jacksonville, FL) 195 446 eyes mice 2 10 months age sampled from colony 400 mice. From group 24 at 4, 9, age, correlations were determined density number RGC axons, thickness, IOP.Mean IOP...
Axon degeneration can arise from metabolic stress, potentially a result of mitochondrial dysfunction or lack appropriate substrate input. In this study, we investigated whether the vulnerability observed during optic neuropathy in DBA/2J (D2) model glaucoma is due to dysfunctional mitochondria impaired delivery axons, latter based on our observation significantly decreased glucose and monocarboxylate transporters D2 nerve (ON), human ON, mice subjected acute injury. We placed both sexes...
Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these are poorly understood. Previous work suggests that anterograde is affected earlier to a larger degree than retrograde transport, yet this has never examined directly vivo. Using combined tract tracing methods, we time-course retinofugal projection pre-glaucomatous (3 month-old) glaucomatous (9-13 month old) DBA/2J...
Neuroinflammation—astrogliosis, microglial activation, and changes in cytokine signaling—is a prominent feature of neurodegenerative disorders. Glaucoma is group chronic conditions that make up the leading cause irreversible blindness worldwide. Neuroinflammation has been postulated to play significant role pathogenesis progression glaucomatous neurodegeneration. Though much known regarding inflammation eye glaucoma, little about activity outside retina where pathologies develop early. We...
Aims: Cellular response to hypoxia can include transition from respiration glycolysis via upregulation of glycolytic enzymes and transporters, as well mitophagy induction eliminate surplus mitochondria. Our purpose was evaluate the impact hypoxia-inducible factor-1α (HIF-1α) stabilization on mitochondrial homeostasis oxidative stress in a chronic model glaucoma. Results: Retina optic nerve (ON) were evaluated young aged DBA/2J (D2) glaucoma mice control strain, DBA/2-Gpnmb+. Hypoxic retinal...
Abstract Mice exhibit a unique wound healing response following spinal cord injury in which the lesion site fills with connective tissue matrix. Previous studies have revealed that axons grow into this matrix, but source of remained unknown. The present study assesses whether any these were result long tract regeneration. C57Bl/6 mice received crush injuries and allowed to survive for 6 weeks 7 months. Biotinylated dextran amine (BDA) was injected somato‐motor cortex trace descending...