Ferroptosis and the eye: bridging the gap between cell death and vision preservation

Ferroptosis, a recently discovered type of programmed cell death (PCD) distinguished by iron overload and lipid peroxidation, differs fundamentally from necrosis, apoptosis, and autophagy. Emerging evidence indicates that ferroptosis is deeply implicated in the disruption of the ocular microenvironment, wherein both structural and immune cells are significantly compromised. Rather than being an isolated cellular event, ferroptosis actively engages in a complex bidirectional crosstalk with the ocular immune system, driving neuroinflammation and tissue degeneration. In this review, we shift the paradigm from traditional disease-specific descriptions to the underlying microenvironmental interactions that dictate ocular health. Furthermore, we systematically evaluate the therapeutic potential of emerging interventions. Specifically, we highlight the latest breakthroughs in utilizing natural and dietary compounds as potent ferroptosis regulators. Crucially, we address current translational limitations by exploring advanced drug delivery systems, such as nanocarriers and hydrogels, designed to effectively overcome the blood-retinal barrier (BRB) and improve targeted efficacy. Ultimately, this review provides a comprehensive roadmap for advancing ferroptosis-targeted therapies from the laboratory to clinical ophthalmology.