Advances in understanding glaucoma pathogenesis: A multifaceted molecular approach for clinician scientists

Eren Ekici; Sasan Moghimi

doi:10.1016/j.mam.2023.101223

Advances in understanding glaucoma pathogenesis: A multifaceted molecular approach for clinician scientists

Mol Aspects Med. 2023 Oct 27:94:101223. doi: 10.1016/j.mam.2023.101223. Online ahead of print.

Authors

Eren Ekici¹, Sasan Moghimi²

Affiliations

¹ T.R. (Republic of Turkey) Ministry of Health, Ankara Etlik City Hospital, Department of Ophthalmology, Ankara, Turkiye. Electronic address: opdrerenekici@gmail.com.
² Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA. Electronic address: sasanimii@yahoo.com.

PMID: 39492376
DOI: 10.1016/j.mam.2023.101223

Abstract

Glaucoma, a leading cause of irreversible blindness worldwide, is a spectrum of neurodegenerative diseases characterized by the gradual deterioration of retinal ganglion cells (RGCs) and optic neuropathy. With complex etiology, glaucoma's major risk factors include elevated intraocular pressure (IOP), advanced age, ethnicity, systemic vascular factors, and genetic predisposition. By 2040, glaucoma is expected to affect over 110 million individuals aged 40 to 80, posing a significant economic burden. Glaucoma can be classified into open-angle, angle-closure, and developmental subtypes, with primary and secondary forms. The disease often progresses silently, gradually impairing the visual field (VF) until it reaches an advanced stage. Understanding the abnormal functional changes associated with glaucoma at the tissue, cellular, molecular, and genetic levels is crucial for comprehending its pathogenesis. This review examines the published data from the past two decades to shed light on the biological mechanisms underlying glaucoma development. The most evident factors in the development of glaucomatous optic neuropathy include elevated IOP, aging, genetic influences, followed by impaired ocular blood flow regulation. These factors are interconnected processes that lead to optic nerve damage, compromised circulation, and structural changes in glial and connective tissues. Contributing factors involve extracellular matrix remodeling, excitotoxicity, nitric oxide, oxidative stress, and neuroinflammation. Ultimately, all types of glaucoma result in RGC dysfunction and loss, causing irreversible visual impairment. While our understanding of glaucoma pathogenesis is evolving, further research is crucial for a comprehensive understanding of glaucoma pathogenesis and the development of effective treatments.

Keywords: Excitotoxicity; Extracellular matrix remodeling; Glaucoma; Intraocular pressure; Ischemia; Lamina cribrosa; Neuroinflammation; Optic nerve head; Oxidative stress; Pathogenesis; Retinal ganglion cell; Vascular dysregulation.

Publication types

Review