The roles of glycerophospholipids in the aging retina and age-related macular degeneration.

Abstract

Glycerophospholipids (GPs) are integral constituents of cellular membranes, and play a crucial role in the regulation of lipid metabolism homeostasis and physiological conditions. However, pathological alterations associated with aging, such as variations in plasma GP concentrations, disruptions in intercellular GP transport, and local accumulation of excessive GPs, have been observed. These changes induce irreversible cellular degeneration, ultimately leading to tissue damage in organs such as the brain and retina. A growing body of evidences has demonstrated that GPs play significant roles in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Similarly, GPs have been implicated in the pathogenesis and progression of age-related macular degeneration (AMD), a degenerative condition affecting the choroid and retinal layers of the eye. Understanding the homeostasis of GP metabolism in the aging retina and in AMD is essential for elucidating the pathogenic processes involved in AMD. In this review, we present a comprehensive overview of the mechanisms of GPs in the aging retina and their correlation with degenerative processes associated with AMD. KEY MESSAGES: What is known Metabolic dysregulation of glycerophospholipids (GPs) plays vital roles in age-related macular degeneration (AMD) and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Patients with age-related neurological disorders exhibit a significantly higher risk of developing AMD compared to healthy individuals, potentially due to shared pathological mechanisms, including mitochondrial metabolic disturbance, chronic inflammation and autophagy dysfunction. What is new The interconnection between multiple GP species and their metabolites has been established to delineate complex pathogenic mechanisms underlying the aging retina and AMD, including cell senescence, autophagy and apoptosis, oxidative stress, inflammation, vascular abnormalities. GPs may serve as potential therapeutic targets to prevent or delay the progression of AMD.