Neuroprotection in glaucoma: Mechanisms beyond intraocular pressure lowering.

James R Tribble, Flora Hui, Heberto Quintero, Sana El Hajji, Katharina Bell, Adriana Di Polo, Pete A Williams

Journal: Molecular aspects of medicine 2023;92():101193

PMID: 37331129

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Abstract

Glaucoma is a common, complex, multifactorial neurodegenerative disease characterized by progressive dysfunction and then loss of retinal ganglion cells, the output neurons of the retina. Glaucoma is the most common cause of irreversible blindness and affects ∼80 million people worldwide with many more undiagnosed. The major risk factors for glaucoma are genetics, age, and elevated intraocular pressure. Current strategies only target intraocular pressure management and do not directly target the neurodegenerative processes occurring at the level of the retinal ganglion cell. Despite strategies to manage intraocular pressure, as many as 40% of glaucoma patients progress to blindness in at least one eye during their lifetime. As such, neuroprotective strategies that target the retinal ganglion cell and these neurodegenerative processes directly are of great therapeutic need. This review will cover the recent advances from basic biology to on-going clinical trials for neuroprotection in glaucoma covering degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation. With an increased understanding of both the basic and clinical mechanisms of the disease, we are closer than ever to a neuroprotective strategy for glaucoma.

Address: Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Department of Optometry & Vision Sciences, The University of Melbourne, Melbourne, Australia.; Department of Neuroscience, University of Montreal, Montreal, Canada; Neuroscience Division, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.; NHMRC Clinical Trials Centre, University of Sydney, Australia; Eye ACP Duke-NUS, Singapore.; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address: [email protected].

DOI: 10.1016/j.mam.2023.101193