Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells

Sergeeva, Elena G.; Rosenberg, Paul A.; Benowitz, Larry I.

doi:10.3389/fncel.2021.666798

Cited by 13 publications

(15 citation statements)

References 178 publications

(234 reference statements)

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“…Peroxynitrite is an oxidant produced by the reaction between nitric oxide (NO) and superoxide radicals. Interestingly, the production of NO after optic nerve injury might act upstream of zinc liberation, leading to accumulation in amacrine cell terminals ( Sergeeva et al, 2021 ). The accumulation of Zn 2+ in the synaptic contacts between the amacrine cells and dendrites of RGCs is one of the earliest events following optic nerve injury ( Benowitz et al, 2017 ).…”

Section: Metal Homeostasis and The Fate Of Rgcsmentioning

confidence: 99%

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

Tang

Zhuo

2021

Front. Cell Dev. Biol.

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Glaucoma is the most substantial cause of irreversible blinding, which is accompanied by progressive retinal ganglion cell damage. Retinal ganglion cells are energy-intensive neurons that connect the brain and retina, and depend on mitochondrial homeostasis to transduce visual information through the brain. As cofactors that regulate many metabolic signals, iron and zinc have attracted increasing attention in studies on neurons and neurodegenerative diseases. Here, we summarize the research connecting iron, zinc, neuronal mitochondria, and glaucomatous injury, with the aim of updating and expanding the current view of how retinal ganglion cells degenerate in glaucoma, which can reveal novel potential targets for neuroprotection.

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Section: Metal Homeostasis and The Fate Of Rgcsmentioning

confidence: 99%

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

Tang

Zhuo

2021

Front. Cell Dev. Biol.

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“…In an optic nerve injury situation, it has been proposed that BCs are involved in RGC protection and axon regeneration indirectly through interactions with ACs. Excitatory neurotransmitter glutamate released by BCs binds to NMDA and AMPA receptors on the post-synaptic membrane of ACs, leading to the latter neurons’ activation, depolarization, Ca 2+ influx, and eventually Zn 2+ accumulation [ 9 ]. In fact, AC-specific blockage of NMDA receptors suppresses mobile Zn 2+ elevation within AC processes after ONC [ 9 ].…”

Section: Synaptic Interactions With Rgcsmentioning

confidence: 99%

“…Excitatory neurotransmitter glutamate released by BCs binds to NMDA and AMPA receptors on the post-synaptic membrane of ACs, leading to the latter neurons’ activation, depolarization, Ca 2+ influx, and eventually Zn 2+ accumulation [ 9 ]. In fact, AC-specific blockage of NMDA receptors suppresses mobile Zn 2+ elevation within AC processes after ONC [ 9 ]. Nevertheless, the direct effects of BCs on axon regeneration still remain unclear.…”

Section: Synaptic Interactions With Rgcsmentioning

confidence: 99%

“…Previously, RGC death and regeneration were commonly considered to be cell-autonomous or influenced by glia. Recently, however, the importance of synaptic interactions between RGC and interneurons, mostly amacrine cells (ACs), has been realized [ 9 ]. Therefore, we summarize recent advances in the interneuron-mediated inhibition of axon regrowth and proposed several hypotheses regarding its potential mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Synaptic or Non-synaptic? Different Intercellular Interactions with Retinal Ganglion Cells in Optic Nerve Regeneration

Zhang

Zhuo

2022

Mol Neurobiol

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Axons of adult neurons in the mammalian central nervous system generally fail to regenerate by themselves, and few if any therapeutic options exist to reverse this situation. Due to a weak intrinsic potential for axon growth and the presence of strong extrinsic inhibitors, retinal ganglion cells (RGCs) cannot regenerate their axons spontaneously after optic nerve injury and eventually undergo apoptosis, resulting in permanent visual dysfunction. Regarding the extracellular environment, research to date has generally focused on glial cells and inflammatory cells, while few studies have discussed the potentially significant role of interneurons that make direct connections with RGCs as part of the complex retinal circuitry. In this study, we provide a novel angle to summarize these extracellular influences following optic nerve injury as “intercellular interactions” with RGCs and classify these interactions as synaptic and non-synaptic. By discussing current knowledge of non-synaptic (glial cells and inflammatory cells) and synaptic (mostly amacrine cells and bipolar cells) interactions, we hope to accentuate the previously neglected but significant effects of pre-synaptic interneurons and bring unique insights into future pursuit of optic nerve regeneration and visual function recovery.

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“…Therefore, RGC axon degeneration has a closed association between mitochondrial function and oxidative stress ( Figure 2 ). Recent studies also showed that the death or survival of RGCs, as well as their ability to regenerate axons, are also influenced by the complex circuitry of the retina and adjacent cells such as amacrine cells, oligodendrocytes, and bipolar cells [ 40 , 43 , 44 ]. Many studies have reported the possible pathophysiology of oxidative stress in RGCs and relevant eye diseases, as we have reviewed below.…”

Section: Mitochondria and Oxidative Stress In Retinal Ganglion Cellsmentioning

confidence: 99%

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

Kang

Liu

Wen³

et al. 2021

Antioxidants

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Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular diseases remain largely unknown. RGCs are a population of central nervous system neurons, with their soma located in the retina and long axons that extend through the optic nerve to form distal terminals and connections in the brain. Because of this unique cytoarchitecture and highly compartmentalized energy demand, RGCs are highly mitochondrial-dependent for adenosine triphosphate (ATP) production. Recently, oxidative stress and mitochondrial dysfunction have been found to be the principal mechanisms in RGC degeneration as well as in other neurodegenerative disorders. Here, we review the role of oxidative stress in several ocular diseases associated with RGC degenerations, including glaucoma, hereditary optic atrophy, inflammatory optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and drug toxicity. We also review experimental approaches using cell and animal models for research on the underlying mechanisms of RGC degeneration. Lastly, we discuss the application of antioxidants as a potential future therapy for the ocular diseases associated with RGC degenerations.

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Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells

Cited by 13 publications

References 178 publications

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

Synaptic or Non-synaptic? Different Intercellular Interactions with Retinal Ganglion Cells in Optic Nerve Regeneration

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

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