scholarly journals Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Atsuko Kimura ◽  
Kazuhiko Namekata ◽  
Xiaoli Guo ◽  
Takahiko Noro ◽  
Chikako Harada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Vision Loss ◽  
Demyelinating Disease ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Elevated Intraocular Pressure ◽  
The Central Nervous System

Glaucoma is a neurodegenerative disease of the eye and it is one of the leading causes of blindness. Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons, namely, the optic nerve, usually associated with elevated intraocular pressure (IOP). Current glaucoma therapies target reduction of IOP, but since RGC death is the cause of irreversible vision loss, neuroprotection may be an effective strategy for glaucoma treatment. One of the risk factors for glaucoma is increased oxidative stress, and drugs with antioxidative properties including valproic acid and spermidine, as well as inhibition of apoptosis signal-regulating kinase 1, an enzyme that is involved in oxidative stress, have been reported to prevent glaucomatous retinal degeneration in mouse models of glaucoma. Optic neuritis is a demyelinating inflammation of the optic nerve that presents with visual impairment and it is commonly associated with multiple sclerosis, a chronic demyelinating disease of the central nervous system. Although steroids are commonly used for treatment of optic neuritis, reduction of oxidative stress by approaches such as gene therapy is effective in ameliorating optic nerve demyelination in preclinical studies. In this review, we discuss oxidative stress as a therapeutic target for glaucoma and optic neuritis.

scholarly journals Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?

2021 ◽  
Vol 13 ◽  
Author(s):  
Jingfei Xue ◽  
Yingting Zhu ◽  
Zhe Liu ◽  
Jicheng Lin ◽  
Yangjiani Li ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Ganglion Cells ◽  
Neuronal Degeneration ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Treatment Plans ◽  
The Central Nervous System ◽  
The Relationship

Neurodegenerative disorders are characterized by typical neuronal degeneration and axonal loss in the central nervous system (CNS). Demyelination occurs when myelin or oligodendrocytes experience damage. Pathological changes in demyelination contribute to neurodegenerative diseases and worsen clinical symptoms during disease progression. Glaucoma is a neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the optic nerve. Since it is not yet well understood, we hypothesized that demyelination could play a significant role in glaucoma. Therefore, this study started with the morphological and functional manifestations of demyelination in the CNS. Then, we discussed the main mechanisms of demyelination in terms of oxidative stress, mitochondrial damage, and immuno-inflammatory responses. Finally, we summarized the existing research on the relationship between optic nerve demyelination and glaucoma, aiming to inspire effective treatment plans for glaucoma in the future.

scholarly journals Retinal Ganglion Cell Transplantation: Approaches for Overcoming Challenges to Functional Integration

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1426
Author(s):  
Kevin Y. Zhang ◽  
Erika A. Aguzzi ◽  
Thomas V. Johnson
Keyword(s):  
Optic Nerve ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Functional Integration ◽  
Experimental Models ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Current State ◽  
Collective Effort ◽  
The Central Nervous System

As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To functionally restore vision, lost RGCs must be replaced. Despite tremendous advancements in experimental models of optic neuropathy that have elucidated pathways to induce endogenous RGC neuroprotection and axon regeneration, obstacles to achieving functional visual recovery through exogenous RGC transplantation remain. Key challenges include poor graft survival, low donor neuron localization to the host retina, and inadequate dendritogenesis and synaptogenesis with afferent amacrine and bipolar cells. In this review, we summarize the current state of experimental RGC transplantation, and we propose a set of standard approaches to quantifying and reporting experimental outcomes in order to guide a collective effort to advance the field toward functional RGC replacement and optic nerve regeneration.

scholarly journals Oxidative Stress in Optic Neuropathies

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1538
Author(s):  
Berta Sanz-Morello ◽  
Hamid Ahmadi ◽  
Rupali Vohra ◽  
Sarkis Saruhanian ◽  
Kristine Karla Freude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Redox System ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oxidative Stress Biomarkers ◽  
Optic Disc Drusen ◽  
Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

The Biomechanical Response of Normal and Glaucoma Human Sclera

2010 ◽  
Author(s):  
Baptiste Coudrillier ◽  
Kristin M. Myers ◽  
Thao D. Nguyen
Keyword(s):  
Retinal Ganglion Cells ◽  
Material Properties ◽  
Visual Information ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Biomechanical Response ◽  
Elevated Intraocular Pressure ◽  
The Relationship ◽  
The Brain

By 2010, 60 million people will have glaucoma, the second leading cause of blindness worldwide [1]. The disease is characterized by a progressive degeneration of the retinal ganglion cells (RGC), a type of neuron that transmits visual information to the brain. It is well know that elevated intraocular pressure (IOP) is a risk factor in the damage to the RGCs [3–5], but the relationship between the mechanical properties of the ocular connective tissue and how it affects cellular function is not well characterized. The cornea and the sclera are collage-rich structures that comprise the outer load-bearing shell of the eye. Their preferentially aligned collagen lamellae provide mechanical strength to resist ocular expansion. Previous uniaxial tension studies suggest that altered viscoelastic material properties of the eye wall play a role in glaucomatous damage [6].

scholarly journals Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

2020 ◽  
Vol 70 (4) ◽  
pp. 618-630 ◽  
Author(s):  
Hong-Kan Zhang ◽  
Yuan Ye ◽  
Kai-Jun Li ◽  
Zhen-ni Zhao ◽  
Jian-Feng He
Keyword(s):  
Oxidative Stress ◽  
Optic Neuritis ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Inflammatory Factors ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects

AbstractOur previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune optic neuritis. However, the therapeutic mechanisms remain unclear. Thus, in this study, a model of oxidative damage in retinal ganglion cells (RGCs) was established to investigate the protective effect of Gp, and its possible influence on oxidative stress in RGCs. Treatment of cells with H2O2 induced RGC injury owing to the generation of intracellular reactive oxygen species (ROS). In addition, the activities of antioxidative enzymes decreased and the expression of inflammatory factors increased, resulting in an increase in cellular apoptosis. Gp helped RGCs to become resistant to oxidation damage by directly reducing the amount of ROS in cells and exerting protective effects against H2O2-induced apoptosis. Treatment with Gp also reduced the generation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased nuclear respiratory factor 2 (Nrf-2) levels so as to increase the levels of heme oxygenase-1 (HO-1) and glutathione peroxidase 1/2 (Gpx1/2), which can enhance antioxidation in RGCs. In conclusion, our data indicate that neuroprotection by Gp involves its antioxidation and anti-inflammation effects. Gp prevents apoptosis through a mitochondrial apoptotic pathway. This finding might provide novel insights into understanding the mechanism of the neuroprotective effects of gypenosides in the treatment of optic neuritis.

scholarly journals Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Reas S. Khan ◽  
Kimberly Dine ◽  
John G. Geisler ◽  
Kenneth S. Shindler
Keyword(s):  
Optic Neuritis ◽  
Demyelinating Disease ◽  
Ganglion Cells ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
High Dose ◽  
Axonal Loss ◽  
Mitochondrial Uncoupling ◽  
The Central Nervous System ◽  
Mitochondrial Uncoupler

The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria’s physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis.

scholarly journals Foveate vision in deep–sea teleosts: a comparison of primary visual and olfactory inputs

2000 ◽  
Vol 355 (1401) ◽  
pp. 1315-1320 ◽  
Author(s):  
Shaun P. Collin ◽  
Darren J. Lloyd ◽  
Hans–Joachim Wagner
Keyword(s):  
Optic Nerve ◽  
Deep Sea ◽  
Ganglion Cells ◽  
Relative Size ◽  
Olfactory Nerve ◽  
Resolving Power ◽  
Retinal Ganglion ◽  
Foveal Vision ◽  
Bias Ratio ◽  
The Central Nervous System

The relative importance of vision in a foveate group of alepocephalid teleosts is examined in the context of a deep–sea habitat beyond the penetration limits of sunlight. The large eyes of Conocara spp. possess deep convexiclivate foveae lined with Müller cells comprising radial shafts of intermediate filaments and horizontal processes. Photoreceptor cell (171.8 × 10 3 rods mm −2 ) and retinal ganglion cell (11.9 × 10 3 cells mm −2 ) densities peak within the foveal clivus and the perifoveal slopes, respectively, with a centro–peripheral gradient between 3:1 (photoreceptors) and over 20:1 (ganglion cells). The marked increase in retinal sampling localized in temporal retina, coupled with a high summation ratio (13:1), suggest that foveal vision optimizes both spatial resolving power and sensitivity in the binocular frontal visual field. The elongated optic nerve head is comprised of over 500 optic papillae, which join at the embryonic fissure to form a thin nervous sheet behind the eye. The optic nerve is divided into two axonal bundles; one receiving input from the fovea (only unmyelinated axons) and the other from non–specialized retinal regions (25% of axons are myelinated), both of which appear to be separated as they reach the visual centres of the central nervous system. Comparison of the number of primary (first–order) axonal pathways for the visual (a total of 63.4 × 10 6 rod photoreceptors) and olfactory (a total of 15.24 × 10 5 olfactory nerve axons) inputs shows a marked visual bias (ratio of 41:1). Coupled with the relative size of the optic tecta (44.0 mm 3 ) and olfactory bulbs (0.9 mm 3 ), vision appears to play a major role in the survival of these deep–sea teleosts and emphasizes that ecological and behavioural strategies account for significant variation in sensory brain structure.

Design of Experiments for Exposure of Astrocytes to Elevated Hydrostatic Pressure and Hypoxia

2008 ◽  
Author(s):  
Shadi Rajabi ◽  
Craig A. Simmons ◽  
C. Ross Ethier
Keyword(s):  
Intraocular Pressure ◽  
Visual Field ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Visual Field Loss ◽  
Retinal Ganglion ◽  
Common Cause ◽  
Elevated Intraocular Pressure

Glaucoma, a chronic optic neuropathy, is the second most common cause of blindness, affecting 67 million people worldwide. The damage in glaucoma occurs at the optic nerve head (ONH), where the axons of the retinal ganglion cells leave the eye posteriorly. Glaucoma is frequently associated with elevated intraocular pressure (IOP), and visual field loss can be prevented by significant lowering of IOP. Hence, the role of pressure in glaucoma is important. Unfortunately, the mechanism by which pressure leads to vision loss in glaucoma is very poorly understood.

Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal ganglion cells in a rat model of optic neuritis

2017 ◽  
Vol 96 ◽  
pp. 1363-1370 ◽  
Author(s):  
Qiang Liu ◽  
Haining Li ◽  
Juan Yang ◽  
Xiaoyan Niu ◽  
Chunmei Zhao ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Retinal Ganglion Cells ◽  
Rat Model ◽  
Ganglion Cells ◽  
Retinal Ganglion

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

2021 ◽  
Vol 15 ◽  
Author(s):  
Elena G. Sergeeva ◽  
Paul A. Rosenberg ◽  
Larry I. Benowitz
Keyword(s):  
Optic Nerve ◽  
Visual Information ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Inflammatory Cells ◽  
Retinal Ganglion ◽  
Ability To Regenerate ◽  
Mature Neurons ◽  
The Central Nervous System ◽  
Extracellular Environment

Visual information is conveyed from the eye to the brain through the axons of retinal ganglion cells (RGCs) that course through the optic nerve and synapse onto neurons in multiple subcortical visual relay areas. RGCs cannot regenerate their axons once they are damaged, similar to most mature neurons in the central nervous system (CNS), and soon undergo cell death. These phenomena of neurodegeneration and regenerative failure are widely viewed as being determined by cell-intrinsic mechanisms within RGCs or to be influenced by the extracellular environment, including glial or inflammatory cells. However, a new concept is emerging that the death or survival of RGCs and their ability to regenerate axons are also influenced by the complex circuitry of the retina and that the activation of a multicellular signaling cascade involving changes in inhibitory interneurons – the amacrine cells (AC) – contributes to the fate of RGCs. Here, we review our current understanding of the role that interneurons play in cell survival and axon regeneration after optic nerve injury.

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