A5076526686- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Connexins and lens biology
- Neuroscience and Neuropharmacology Research
- Ion Channels and Receptors
- Visual perception and processing mechanisms
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disorders and Treatments
- Ocular Surface and Contact Lens
- Neural dynamics and brain function
- Retinopathy of Prematurity Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Nerve injury and regeneration
- Corneal Surgery and Treatments
- Biochemical effects in animals
- Pain Mechanisms and Treatments
- Neuroscience and Neural Engineering
- Corneal surgery and disorders
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- Axon Guidance and Neuronal Signaling
- Retinal and Optic Conditions
- Color Science and Applications
Vanderbilt University
2012-2025
Vanderbilt University Medical Center
2015-2024
Vanderbilt Health
2010-2023
Sandia National Laboratories California
2012-2015
Nashville Oncology Associates
2015
National Technical Information Service
2012
Sensor Electronics (United States)
2012
Sandia National Laboratories
2012
Office of Scientific and Technical Information
2012
Veterans Health Administration
2010
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...
Purpose.: Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Animal models often involve techniques IOP elevation that are surgically invasive. Here the authors describe a novel and relatively simple method inducing highly consistent, modest, repeatable in rats mice. Methods.: was elevated unilaterally by injection of polystyrene microbeads into anterior chamber to occlude aqueous outflow (2.5–7 μL) mice (1 μL). The fellow eye received equivalent saline as internal...
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...
At 96 weeks after unilateral intravitreal injection of rAAV2/2- ND4 , vision improved in both eyes 78% subjects affected with LHON.
Perception of hue is opponent, involving the antagonistic comparison signals from different cone types. For blue versus yellow opponency, antagonism first evident at a ganglion cell with firing that increases to stimulation short wavelength-sensitive (S) cones and decreases middle (M) long (L) cones. This cell, termed blue–yellow (B–Y), has distinctive morphology dendrites in both ON OFF strata inner plexiform layer (Dacey Lee, 1994). Here we report synaptic circuitry its spatial density....
Glaucomatous optic neuropathy causes blindness through the degeneration of retinal ganglion cells (RGCs) and their axons, which comprise nerve. Glaucoma traditionally is associated with elevated intraocular pressure, but often occurs or may progress pressure in normal range. Like other diseases CNS, a subset glaucoma has been proposed to involve an autoimmune component help explain loss RGCs absence pressure. One hypothesis involves heat shock proteins (HSPs), because increased serum levels...
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...
purpose. Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to sensing and Ca2+-dependent death other systems, also pressure-induced RGC this contribution involves Ca2+. methods. trpv1 mRNA expression RGCs was probed with use of PCR TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin)...
To characterize a glaucoma model of mice, the authors adopted and modified method inducing chronic elevation intraocular pressure (IOP) by anterior chamber injection polystyrene microbeads.Chronic IOP was induced unilaterally in adult C57BL/6J mice injecting microbeads to chamber. Effectiveness different sizes (small, 10 μm; large, 15 μm) on compared, measured every other day using tonometer. After maintaining elevated for 2, 4, or 8 weeks, degree RGC axon degeneration assessed...
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...
The authors investigated the contributions of transient receptor potential vanilloid-1 (TRPV1) and Ca(2+) to microglial IL-6 nuclear factor kappa B (NFkappaB) translocation with elevated hydrostatic pressure.The first examined colocalization microglia marker Iba-1 in DBA/2 mouse model glaucoma establish relevance. They isolated from rat retina maintained them at ambient or (+70 mm Hg) pressure vitro used ELISA immunocytochemistry measure changes concentration NFkappaB induced by chelator...
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,...
Diseases of the brain involve early axon dysfunction that often precedes outright degeneration. Pruning dendrites and their synapses represents a potential driver axonopathy by reducing activity. Optic nerve degeneration in glaucoma, world's leading cause irreversible blindness, involves stress to retinal ganglion cell (RGC) axons from sensitivity intraocular pressure (IOP). This also influences survival RGC excitatory retina. Here we tested individual RGCs identified type relationship...
Significance Astrocytes respond to neuronal energy needs by mobilizing metabolic stores. How these resources are mobilized during neurodegeneration, especially in nearby regions that not actively degenerating, could impact new therapeutic approaches. We modeled neurodegeneration glaucoma and measured how metabolites mobilize through astrocyte networks. elevated pressure one eye determined astrocyte-derived the opposite nerve responded. Remarkably, networks expand redistribute along distances...
How neurons respond to stress in degenerative disease is of fundamental importance for identifying mechanisms progression and new therapeutic targets. Members the transient receptor potential (TRP) family cation-selective ion channels are candidates mediating signals, since different subunits transduce a variety stimuli relevant both normal pathogenic physiology. We addressed this possibility TRP vanilloid-1 (TRPV1) subunit by comparing how optic projection Trpv1(-/-) mice age-matched C57...