Metabolic dysregulation in glaucoma.

Abstract

Glaucoma is a multifactorial neurodegenerative disorder characterised by the progressive loss of retinal ganglion cells, ultimately leading to irreversible blindness worldwide. Recent research highlights metabolic dysregulation as a crucial factor in the pathophysiology of glaucoma. This review examines the intricate relationship between metabolic processes and glaucoma, with a focus on key mechanisms such as mitochondrial dysfunction, lipid metabolism, glucose metabolism, and the roles of specific metabolites. Mitochondrial dysfunction is commonly observed in glaucoma, leading to impaired energy production that compromises cellular viability. Alterations in lipid metabolism, including changes in fatty acid profiles and lipid peroxidation, contribute to cellular injury and apoptosis of retinal ganglion cells. Moreover, disturbances in glucose metabolism, such as reduced glycolytic activity, affect energy availability and neurotrophic support that are vital for retinal ganglion cells survival. The review also explores the roles of specific metabolites, including lactate and glutamate, in the context of retinal ganglion cells health, and how their dysregulation may exacerbate glaucomatous damage. Additionally, the interplay between metabolic dysregulation and elevated intraocular pressure is analysed, particularly with regard to its impact on ocular blood flow and retinal health. Understanding these metabolic mechanisms is essential for identifying potential therapeutic strategies. By deepening our understanding of the metabolic foundations of glaucoma, new avenues for effective treatments may arise, addressing the multifactorial nature of this complex disease and improving patient outcomes.