Retinal Ganglion Cell Axotomy Induces an Increase in Intracellular Superoxide Anion

Lieven, Christopher J.; Hoegger, Mark J.; Schlieve, Christopher R.; Levin, Leonard A.

doi:10.1167/iovs.05-0921

Cited by 92 publications

(97 citation statements)

References 30 publications

(40 reference statements)

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“…Among other proposed mechanisms such as those initiated by neurotrophin deprivation (Pease et al, 2000) or TNF-α signaling , which is also associated with oxidative injury, RGC death after axonal injury has been proposed to be dependent on ROS generation in such a way that these oxidants act as intracellular signaling molecules responsible for transforming the information from the damaged axon into a RGC death signal. Based on the observation of increased superoxide anion in RGCs, likely proximal to caspase activation, ROS generation has been suggested to be a parallel system to neurotrophin deprivation for signaling RGC death after axonal injury (Lieven et al, 2006;Nguyen et al, 2003;Swanson et al, 2005). On the other hand, ROS production has been involved in growth factor signaling through the observations that pre-treatment with antioxidants or overexpression of a ROS-scavenging enzyme block tyrosine phosphorylation (Sundaresan et al, 1995;Suzukawa et al, 2000).…”

Section: Oxidative Stress In Widespread Damage To Rgcs In Glaucomamentioning

confidence: 99%

Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

Tezel

2006

Progress in Retinal and Eye Research

611

449

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Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. Although ROS are essential participants in cell signaling and regulation, when their cellular production overwhelms the intrinsic antioxidant capacity, damage to cellular macromolecules such as DNA, proteins, and lipids ensues. Such a state of "oxidative stress" is thought to contribute to the pathogenesis of a number of neurodegenerative diseases. Growing evidence supports the involvement of oxidative stress as a common component of glaucomatous neurodegeneration in different subcellular compartments of retinal ganglion cells (RGCs). Besides the evidence of direct cytotoxic consequences leading to RGC death, it also seems highly possible that ROS are involved in signaling RGC death by acting as a second messenger and/or modulating protein function by redox modifications of downstream effectors through enzymatic oxidation of specific amino acid residues. Different studies provide cumulating evidence, which supports the association of ROS with different aspects of the neurodegenerative process. Oxidative protein modifications during glaucomatous neurodegeneration increase neuronal susceptibility to damage and also lead to glial dysfunction. Oxidative stress-induced dysfunction of glial cells may contribute to spreading neuronal damage by secondary degeneration. Oxidative stress also promotes the accumulation of advanced glycation end products in glaucomatous tissues. It is also evident that oxidative stress takes part in the activation of immune response during glaucomatous neurodegeneration, as ROS stimulate the antigen presenting ability of glial cells and also function as co-stimulatory molecules during antigen presentation. By discussing current evidence, this review provides a broad perspective on cellular mechanisms and potential consequences of oxidative stress in glaucoma.

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Section: Oxidative Stress In Widespread Damage To Rgcs In Glaucomamentioning

confidence: 99%

Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

Tezel

2006

Progress in Retinal and Eye Research

611

449

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“…1 Two different probes were used, of which hydroethidium is one of the more commonly used. In the presence of superoxide, it forms a moiety, oxy-ethidium, which binds to DNA and changes its emission spectrum.…”

Section: Fluorescence Imaging Of Retinal Ganglion Cells In Vitromentioning

confidence: 99%

“…1 In the rat, for example, only half of the RGCs die over 7 days after axotomy, and this asynchronous and slow death rate occurred even when there was very abrupt injury, such as the complete transection of all axons. 5 The superoxide increase was not just a phenomenon related to dissociation, but a result of the axotomy.…”

Section: Superoxide Rise In Axotomized Retinal Ganglion Cellsmentioning

confidence: 99%

“…The rise after axotomy was not blocked by neurotrophic factors and cyclic AMP and therefore appeared to be at least partially independent of these factors (ie not caused by neurotrophin deprivation). 1 Among several inhibitors of intracellular superoxide generation studied, only antimycin A, which inhibits complex III of the mitochondrial electron transport chain, blocked the increase in superoxide. This finding demonstrates that the superoxide is generated in the mitochondrial electron transport chain, and that it could act in parallel to neurotrophic deprivation for signalling cell death after axonal injury.…”

Section: Superoxide Rise In Axotomized Retinal Ganglion Cellsmentioning

confidence: 99%

“…A specific reactive oxygen species (ROS), superoxide anion, may act as an intracellular messenger for signalling RGC death, as an additional mechanism. 1 Research suggests critical sulphydryls (molecular groups that include a bonded sulphur and hydrogen atom), probably on proteins, may be downstream regulators of this signal pathway. 2 Monitoring the levels of these two potential surrogate biomarkers of RGC apoptosis could be a useful tool to detect early events in optic neuropathies.…”

Section: Introductionmentioning

confidence: 99%

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Tools for studying early events in optic neuropathies

Lieven

Levin

2007

Eye

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Most optic nerve injuries are axonal. Neurotrophin deprivation induces death of retinal ganglion cells (RGCs) in such cases, but this is probably not the only mechanism that causes their death. Various fluorophores and agents that block mitochondrial electron transport have been used to show that superoxide generated in the mitochondrial electron transport chain could act, in addition to neurotrophin deprivation, to signal cell death after axonal injury. More specifically, sulphydrylsFprobably on proteinsFare downstream regulators of this signalling pathway, as shown by the neuroprotective effects of inhibition of sulphydryl oxidation by tris(2-carboxyethyl)phosphine in in vivo rat models. Other tools used to study early events in RGC death include novel reducing agents, inducible superoxide dismutase, and differentiation of the RGC-5 cell line.

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