Eye and vision
SLC7A11-mediated disulfidptosis underlies the pathogenesis of proliferative diabetic retinopathy
By Yuan B, Chen S, Liu J and 11 others.
Abstract
Background
We investigated the role of disulfidptosis, a recently identified form of cell death, in the pathogenesis of proliferative diabetic retinopathy (PDR) and explore the function of the cystine/glutamate antiporter, SLC7A11, as a key mediator and potential therapeutic target.
Methods
Bioinformatic analysis was used to screen disulfidptosis-related genes from public RNA sequencing datasets, which were subsequently validated in PDR fibrovascular membranes (FVMs) and vitreous humor via immunofluorescence and western blotting analysis. Human retinal microvascular endothelial cells (HRMECs) were cultured in normal or high-glucose media, and SLC7A11 expression modulated using small interfering RNA or lentiviral overexpression. Angiogenesis was assessed via proliferation, migration, and tube formation assays. Disulfidptosis was induced via acute glucose deprivation in high-glucose-adapted HRMECs and biochemically evaluated. A streptozotocin-induced diabetic mouse model was utilized to assess SLC7A11 expression in vivo, and therapeutic efficacy was tested through weekly intravitreal lavage with glucose-free versus glucose-replete solutions.
