Abstract
Iron is an essential component in many biological processes in the human body. It is critical for the visual phototransduction cascade in the retina. However, excess iron can be toxic. Iron accumulation and reduced efficiency of intracellular antioxidative defense systems predispose the aging retina to oxidative stress-induced cell death. Age-related macular degeneration (AMD) is characterized by retinal iron accumulation and lipid peroxidation. The mechanisms underlying AMD include oxidative stress-mediated death of retinal pigment epithelium (RPE) cells and subsequent death of retinal photoreceptors. Understanding the mechanism of the disruption of iron and redox homeostasis in the aging retina and AMD is crucial to decipher these mechanisms of cell death and AMD pathogenesis. The mechanisms of retinal cell death in AMD are an area of active investigation; previous studies have proposed several types of cell death as major mechanisms. Ferroptosis, a newly discovered programmed cell death pathway, has been associated with the pathogenesis of several neurodegenerative diseases. Ferroptosis is initiated by lipid peroxidation and is characterized by iron-dependent accumulation. In this review, we provide an overview of the mechanisms of iron accumulation and lipid peroxidation in the aging retina and AMD, with an emphasis on ferroptosis.
Highlights
Iron is the most abundant redox-active heavy metal and is indispensable for several biological processes [1]
Specific components of ferroptosis implicated in agerelated macular degeneration (AMD) pathogenesis include reactive oxygen species (ROS) production, iron accumulation, and lipid peroxidation
Ferroptosis was implicated in retinal cell death before the cell death processes were discovered [126, 146, 232, 233, 281-283]
Summary
Iron is the most abundant redox-active heavy metal and is indispensable for several biological processes [1]. Hepc is expressed in photoreceptors, Müller cells, and the RPE, suggesting that the retina may produce it for local iron regulation [92]. Hepc expression is affected by multiple stimuli including iron level, erythropoiesis rate, inflammation, hypoxia, and oxidative stress [95], through cell surface proteins including HFE, TfR2, hemojuvelin (Hjv), matriptase2, and interleukin 6 (IL-6) [96].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
