Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection

Abstract

Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG), the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure (IOP) is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer (RNFL) defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy (GON).

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

“…OCT was performed as an indicator of progressive neural retinal pathology in animal models of retinal degeneration [38, 39]. In the present study, we found a significant reduction in overall retinal thickness as well as all four quadrants, depending on the OCT scanning, in db/db mice when compared with control mice at the age of 28 weeks.…”

Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis Through the Akt and PERK Pathways

“…In retinal disease such as retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and glaucoma, an insufficient supply of oxygen or nutrients, may occur during conditions of disturbed hemodynamics or vascular defects, results in highly impaired cellular oxygen balance, and retinal neurons become hypoxic (Kaur et al, 2009, 2012; Munemasa and Kitaoka, 2012). Among the retinal neurons, retinal ganglion cells (RGCs) are the predominant components that undergo hypoxic injury (Abu-El-Asrar et al, 2004; Caprara and Grimm, 2012; Munemasa and Kitaoka, 2012), for they are the ultimate neurons in retina that consume large quantities of energy to convey visual information to the brain (Sanes and Masland, 2015). Hypoxia-related disorders enhance or induce the death of RGCs in the retina, resulting in irreversible vision loss, most of which through apoptosis (Kaur et al, 2009; Yang et al, 2013).…”

Imaging of retinal ganglion cells in glaucoma: pitfalls and challenges

“…In glaucoma, RGCs might die not only because of axonal degradation but also because of the activation of glial cells and the oxidative stress of immunological processes (Munemasa and Kitaoka 2012). The relative importance of these mechanisms is unknown.…”