Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis.

Atsuko Kimura,Chikako Harada,Kazuhiko Namekata,Takayuki Harada,Takahiko Noro,Xiaoli Guo

doi:10.1155/2017/2817252

Abstract

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.

Highlights

Glaucoma is a neurodegenerative disease of the eye and it is one of the major causes of irreversible blindness
There is a strong association between optic neuritis and multiple sclerosis (MS), an acute inflammatory demyelinating disease of the central nervous system (CNS), in which optic neuritis is the initial presentation of MS for approximately 20% of MS patients and a risk of developing MS by 15 years after the onset of optic neuritis is 50% [5]
We have previously reported that deletion of the Apoptosis Signal-Regulating Kinase 1 (ASK1) gene prevents retinal ganglion cells (RGCs) death in various mouse models of glaucoma, including retinal ischemia, optic nerve injury (ONI), and GLAST KO mice (GLAST/ASK1 double KO mice) [15, 35, 36]

Summary

Introduction

Glaucoma is a neurodegenerative disease of the eye and it is one of the major causes of irreversible blindness. Optic neuritis is a demyelinating inflammation of the optic nerve and it typically affects young adults ranging from 18 to 45 years of age. Patients usually present with an acute reduction of visual acuity, orbital pain exacerbated by eye movements, dyschromatopsia, and an afferent papillary defect, with or without swelling of the optic nerve head. There is a strong association between optic neuritis and multiple sclerosis (MS), an acute inflammatory demyelinating disease of the central nervous system (CNS), in which optic neuritis is the initial presentation of MS for approximately 20% of MS patients and a risk of developing MS by 15 years after the onset of optic neuritis is 50% [5]. We discuss the role of oxidative stress in the pathogenesis of glaucoma and optic neuritis and how we can target oxidative stress for treatment of these two disease conditions

Oxidative Stress and Glaucoma

Inhibition of Oxidative Stress for Treatment of Glaucoma

Oxidative Stress and Optic Neuritis

Inhibition of Oxidative Stress for Treatment of Optic Neuritis

Findings

Conclusions