Research advances on ferroptosis in retinal fibrotic diseases

Retinal fibrotic diseases represent a class of fundus disorders with profound impacts on visual function; if not treated promptly and effectively, they can lead to visual impairment or even blindness. Currently recognized retinal fibrotic conditions are characterized by retinal fibrosis, involving a pathological process manifested by chronic inflammatory responses, synergistic induction by transforming growth factor-β and connective tissue growth factor, fibroblast proliferation, and excessive extracellular matrix deposition, ultimately culminating in retinal scar formation and visual damage. Ferroptosis is a distinct form of programmed cell death, differing from apoptosis and necrosis, and is closely associated with various metabolic disorders. Ferroptosis is regulated by glutathione peroxidase 4, a key factor that functions not only as a pivotal antioxidant enzyme but also participates in the pathogenesis of multiple diseases. This article systematically elucidates the molecular mechanisms underlying ferroptosis, the functional significance of the critical ferroptosis regulator glutathione peroxidase 4, and the role of ferroptosis in proliferative retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and proliferative vitreoretinopathy, thereby exploring its potential clinical applications.