Molecular Pathways of Glaucoma Progression: Current Perspectives

Abstract

Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell (RGC) degeneration and irreversible vision loss. Despite extensive research, the molecular mechanisms underlying glaucoma pathogenesis remain incompletely understood. Recent studies highlight the crucial role of non-coding RNAs (ncRNAs) in modulating key pathways associated with trabecular meshwork (TM) dysfunction, retinal neurodegeneration, and fibrotic remodeling. This review provides a comprehensive analysis of the involvement of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in glaucoma progression. We discuss their regulatory influence on pathways such as the TGF-β, PI3K/AKT, MAPK, and Wnt/β-catenin signaling cascades, which are implicated in oxidative stress, extracellular matrix (ECM) remodeling, apoptosis, and fibrosis. Notably, ncRNAs such as miR-29b, miR-200a, and MALAT1 exhibit differential expression patterns in glaucomatous tissues and modulate critical cellular processes that impact intraocular pressure (IOP) regulation and RGC survival.
Furthermore, we explore the potential of ncRNAs as diagnostic biomarkers and therapeutic targets for glaucoma. While ncRNA-based therapies hold promise, challenges such as delivery efficiency, immune responses, and target specificity must be addressed before clinical translation. Future research should focus on elucidating the precise molecular interactions of ncRNAs, optimizing drug delivery systems, and conducting large-scale clinical studies to validate their therapeutic potential. Understanding the intricate network of ncRNA-mediated regulation in glaucoma could pave the way for novel, targeted treatment strategies, ultimately improving patient outcomes and preserving vision.