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...

In glaucoma, the optic nerve head (ONH) is principal site of initial axonal injury, and elevated intraocular pressure (IOP) predominant risk factor. However, responses ONH to IOP are unknown. Here authors use a rat glaucoma model characterize gene expression changes associated with early injury.Unilateral elevation was produced in rats by episcleral vein injection hypertonic saline. mRNA extracted, retrobulbar cross-sections were graded for degeneration. Gene determined microarray...

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...

Brimonidine is a common drug for lowering ocular pressure and may directly protect retinal ganglion cells in glaucoma. The disease involves early loss of cell transport to brain targets followed by axonal somatic degeneration. We examined whether brimonidine preserves abates degeneration rats with elevated induced laser cauterization the episcleral veins.Ocular was unilaterally 90% period 8 weeks post- cauterization. During this time, (1mg/kg/day) or vehicle (phosphate-buffered saline)...

Astrocytes provide metabolic, structural, and synaptic support to neurons in normal physiology also contribute widely pathogenic processes response stress or injury. Reactive astrocytes can undergo cytoskeletal reorganization increase migration through changes intracellular Ca 2+ mediated by a variety of potential modulators. Here we tested whether isolated retinal following mechanical injury (scratch wound) involves the transient receptor vanilloid‐1 channel (TRPV1), which contributes...

Progression of neurodegeneration in disease and injury is influenced by the response individual neurons to stressful stimuli whether this includes mechanisms counter declining function. Transient receptor potential (TRP) cation channels transduce a variety disease-relevant can mediate diverse stress-dependent changes physiology, both presynaptic postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates...

We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Bilateral ocular hypertension was induced mice by injecting microbeads into anterior chamber. Hypertensive received NS loaded with hypotensive drugs via intravitreal injection and IOP monitored. Retinal deposition retinal ganglion cell (RGC) uptake Neuro-DiO were following Neuro-DiO-NS using confocal...

Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease causes vision loss through the degeneration retinal ganglion cell neurons their axons in nerve. Using an inducible model glaucoma, we elevated IOP squirrel monkey (Saimiri boliviensis) using intracameral injection 35 μm polystyrene microbeads measured common pathogenic outcomes projection. A 42% elevation over 28 weeks reduced anterograde transport fluorescently-labeled...

Abstract Background Ischemia within the optic nerve head (ONH) may contribute to retinal ganglion cell (RGC) loss in primary open angle glaucoma (POAG). has been reported increase neurotrophin and high affinity Trk receptor expression by CNS neurons glial cells. We have previously demonstrated lamina cribrosa (LC) region of ONH. To determine if ischemia alters protein cells from human LC, cultured LC ONH astrocytes were exposed 48 hours oxygen-glucose deprivation (OGD). Also OGD followed 24...

Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease the leading cause irreversible blindness worldwide. Early progression in glaucoma involves dysfunction retinal ganglion cell (RGC) axons, which comprise nerve. Deficits anterograde transport along RGC axons central visual structures precede outright degeneration, preventing these deficits efficacious at abating subsequent progression. HE3286 synthetic sterol derivative...

Glaucoma is an age-related neurodegenerative disease that commonly associated with sensitivity to intraocular pressure. The selectively targets retinal ganglion cells (RGCs) and constituent axons. RGC axons are rich in voltage-gated sodium channels, which essential for action potential initiation regeneration. Here, we identified voltage-dependent channel, NaV1.2, the retina, examined how this channel contributes light responses, monitored NaV1.2 mRNA protein expression retina during...

Abstract Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). Early progression involves retinal ganglion cell (RGC) axon dysfunction that precedes frank degeneration. Previously we demonstrated p38 MAPK inhibition abates axonal slows degeneration in the inducible microbead occlusion model glaucoma rat. Here, assessed neuroprotective effect topical eye delivery inhibitor BIRB 796 three models (microbead rat squirrel monkey genetic...