Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. The time course of cell death is variable and depends in part on the degree injury sustained. Decreasing reactive oxygen species (ROS) levels or shifting redox state to reduction promotes survival RGCs tissue culture axotomy. It was hypothesized that a specific ROS, superoxide anion, acts as an intracellular signaling molecule for RGC axotomy.Intracellular were measured dissociation retrograde-labeled rat with use...

Cell lines are frequently used to elucidate mechanisms of disease pathophysiology. Yet extrapolation results with cell neurodegenerative disorders is difficult because they mitotic and usually have other non-neuronal properties. The RGC-5 line has many features retinal ganglion cells (RGCs). Despite its expression Thy-1 NMDA receptors, as found in primary RGCs, this line's ability proliferate appearance differentiate it from central neurons, complicating use for the study neuronal survival,...

J. Neurochem. (2011) 118 , 1075–1086. Abstract The reactive oxygen species (ROS) superoxide has been recognized as a critical signal triggering retinal ganglion cell (RGC) death after axonal injury. Although the downstream targets of are unknown, chemical reduction oxidized sulfhydryls shown to be neuroprotective for injured RGCs. On basis this, we developed novel phosphine‐borane complex compounds that permeable and highly stable. Here, report our lead compound, bis (3‐propionic acid methyl...

The signaling of retinal ganglion cell (RGC) death after axotomy is partly dependent on the generation reactive oxygen species. Shifting RGC redox state toward reduction protective in a dissociated mixed culture model axotomy. hypothesis for current study was that tris(2-carboxyethyl)phosphine (TCEP), sulfhydryl reductant, would protect RGCs rat optic nerve crush axotomy.RGCs postnatal day 4 to 5 Long-Evans rats were retrogradely labeled with fluorescent tracer DiI. At approximately 8 weeks...

Abstract Background Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested retinal ganglion cells (RGCs), a central neuron contained within the retina. Given that RGCs use superoxide intracellular signaling after axotomy, and LHON increase levels...

Retinal ganglion cells (RGCs) die as a result of axonal injury in variety optic neuropathies, including glaucoma. Reactive oxygen species (ROS) act intracellular signaling molecules and initiate apoptosis nerve growth factor-deprived sympathetic neurons axotomized RGCs. Determination the role specific ROS relies on use small molecule or protein scavengers with various degrees specificity. The pro- anti-cell-death effect several generating scavenging systems cultured RGCs was correlated their...

Purpose RGC-5 cells undergo differentiation into a neuronal phenotype with low concentrations of staurosporine. Although the cell line was initially thought to be retinal ganglion origin, recent evidence suggests that could have been result contamination 661W mouse cone photoreceptor cells. This raised possibility multipotent and differentiated phenotype. Methods cells, non-neuronal astrocytes, endothelial pericytes, M21 melanoma K562 chronic myelogenous leukemia Daudi Burkitt lymphoma were...

Purpose.: Light-induced oxidative stress is an important risk factor for age-related macular degeneration, but the downstream mediators of photoreceptor and retinal pigment epithelium cell death after photic injury are unknown. Given our previous identification sulfhydryl/disulfide redox status as a in survival, we hypothesized that formation one or more disulfide-linked homo- hetero-dimeric proteins might signal light-induced injury. Methods.: Two-dimensional (non-reducing/reducing) gel...

To study the role of mitochondrial permeability transition pore (PTP) in apoptosis axotomized retinal ganglion cells (RGCs) vitro.Primary rat cultures containing DiI-labeled RGCs were treated with pharmacological agents that modulate PTP. Ratiometric imaging membrane potential (DeltaPsi(m)) conducted on similarly cultures, dual-emission probe JC-1, and correlation results viability experiments determined.The peripheral benzodiazepine receptor agonist PK11195 induced RGC death, but this was...

Exposure to radiation can damage endothelial cells in the irradiated area via production of reactive oxygen species. We synthesized phosphine–borane complexes that reduce disulfide bonds and had previously been shown interfere with redox-mediated signaling cell death. hypothesized this class drugs could downstream effects oxidative stress after irradiation rescue from damage. Cultured bovine aortic were plated for clonogenic assay prior exposure varying doses a 137Cs irradiator treated...

Central neurons undergo cell death after axotomy. One of the signaling pathways for this process is oxidative modification one or more critical sulfhydryls in association with superoxide generation within mitochondria. Agents that reduce oxidized are neuroprotective axotomized retinal ganglion cells, and we hypothesized occurs via reversal effects mitochondrial-produced superoxide. To study this, measured ability novel borane-phosphine complex drugs bis(3-propionic acid methyl...

Phosphine-borane complexes are recently developed redox-active drugs that neuroprotective in models of optic nerve injury and radioprotective endothelial cells. However, a single dose these compounds is short-lived, necessitating the development sustained-release formulations novel molecules. We screened library biodegradable co- non-block polyester polymer systems for release incorporated phosphine-borane to evaluate them as drug delivery use chronic disease. Bis(3-propionic acid methyl...