Biomarkers for glaucoma: from the lab to the clinic

Abstract

Glaucoma, a leading cause of irreversible blindness worldwide, is often not diagnosed until many years after disease onset. Early and objective diagnostic measures are yet missing. Besides the main risk factor, an elevated intraocular pressure (IOP), age, sex, and ethnicity are known to affect disease progression and severity. Furthermore, oxidative stress, elevated glutamate concentrations, and an autoimmune component are considered possible risk factors. We could identify several potential proteomic biomarkers in glaucoma and examine distinct changes in the glaucomatous human retina proteome. Using an experimental autoimmune glaucoma animal (EAG) model we could demonstrate an IOP-independent loss of retinal ganglion cells (RGC), which is accompanied by antibody depositions and increased levels of microglia. In a different animal model we showed that intermittent IOP elevations provoke neurodegeneration in the optic nerve and the retina and elicit changes of IgG autoantibody reactivities. The correlation between neuronal damage and changes in autoantibody reactivity suggests that autoantibody profiling could be a useful biomarker for glaucoma. In vivo studies on neuroretinal cells and porcine retinal explants demonstrated a protective effect of antibodies (eg, anti-GFAP) on RGC, which seems to be the result of reduced stress levels in the retina. We conclude that the absence of some autoantibodies in glaucoma patients reflects a loss of the protective potential of natural autoimmunity and may thus encourage neurodegenerative processes. Concluding, autoantibody profiles resemble useful biomarkers for diagnosis, progression and severity of glaucoma. Future longitudinal studies will help to improve early detection and enable better monitoring of disease progression.

Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage

“…There are multiple risk factors associated with glaucoma [ 3 , 4 , 5 , 6 , 7 , 8 ], with elevated intraocular pressure (IOP) and aging being two of the more prominent ones [ 9 , 10 , 11 ]. Elevated IOP damages the axons of retinal ganglion cells (RGCs) that make up the optic nerve, eventually causing RGC dysfunction and loss and resulting in blindness [ 2 , 12 ]. Glaucoma is commonly treated with topically-applied IOP-lowering drugs that are well tolerated and effective in managing IOP [ 11 ].…”

“…However, even when IOP is managed well, the disease can progress, resulting in significant vision loss. It is reported that more than 10% of patients become completely blind in at least one eye [ 3 , 12 , 13 , 14 ]. It is thus important to develop therapeutic approaches that directly protect RGCs in an IOP-independent manner.…”

Rational Basis for Nutraceuticals in the Treatment of Glaucoma

“…Glaucoma is a neurodegenerative disease characterized by retinal ganglion cells (RGC) death, typical visual field defect and eventual blindness [ 1 ]. Elevated intraocular pressure (IOP), aging, genetic, epigenetic and environmental factors are among a number of recognized risk factors for glaucoma [ 2 , 3 ]. Glaucoma is thus a progressive optic neuropathy with complex pathophysiology and RGC loss in glaucoma remains incompletely understood [ 4 ].…”

Agonistic β2-Adrenergic Receptor Autoantibodies Characterize the Aqueous Humor of Patients With Primary and Secondary Open-Angle Glaucoma

“…Specific AAb patterns that reportedly depend on the glaucoma subtype are under investigation (36). As b2-agAAb adrenergic activity was observed in AH of POAG and SOAG and as these did not correlate with the routine glaucoma follow-up parameters, these data might indicate that b2-agAAb are involved in very early stages of glaucoma pathogenesis by shared pathophysiologic mechanisms.…”