Organelle Crosstalk: Mitochondria and Endoplasmic Reticulum in Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss characterized by progressive retinal pigment epithelium (RPE) dysfunction, mitochondrial damage, oxidative stress, and chronic inflammation. While mitochondrial dysfunction is a known contributor to AMD, the contribution of the endoplasmic reticulum (ER) has not been fully explored. Mitochondrial associated membranes (MAMs) are regions of the mitochondria which are in direct contact with the ER and are critical areas for regulating essential cellular functions including calcium signaling, mitochondrial dynamics, and apoptosis. Dysfunction of these critical sites may lead to progressive retinal degeneration through the production of reactive oxygen species (ROS), calcium overload, and inflammasome activation in RPE cells. The study was conducted as a comprehensive critical review article on the subject. Findings are reported on the connection between the mitochondria and ER, specifically through MAM dysfunction, in macular degeneration. Overall, this critical review article discusses the pathophysiology of macular degeneration with the mechanistic insights into MAM deregulation and decoding the structural and functional breakdown of MAMs. Understanding the role of MAM-mediated signaling in AMD may identify potential therapeutic targets aimed at restoring mitochondrial resilience and retinal homeostasis.