Research Applications for Striatech Products

Cataract

Publications on Cataract

Cell Death & Disease (Feb 03, 2025) Enhanced ferroptosis sensitivity promotes the formation of highly myopic cataract via the DDR2-Hippo pathway

Guo D, Du Y, Liu X, Li D, Wei L, Zhu X

DOI: 10.1038/s41419-025-07384-8 >>

Featured image for “Enhanced ferroptosis sensitivity promotes the formation of highly myopic cataract via the DDR2-Hippo pathway”

This study investigates the role of ferroptosis in highly myopic cataract (HMC) development, a leading cause of blindness in working-age individuals. Researchers found elevated levels of Fe2+ and lipid peroxidation in HMC lens epithelia, indicating increased vulnerability to ferroptosis. The study identified upregulated expression of DDR2 as a key factor enhancing ferroptosis sensitivity through the Src-Hippo pathway. In a mouse model, highly myopic eyes showed higher sensitivity to RSL3, a ferroptosis inducer, resulting in more severe nuclear lens opacities. These effects could be mitigated by inhibitors of either ferroptosis or DDR2. An infrared Photorefractor was used to assess the refractive state of mice, ensuring only those with less than 1.00 D of refractive disparity between eyes were included in the study1. These findings provide new insights into HMC formation and potential therapeutic interventions.

Highly myopic cataract (HMC) is a leading cause of blindness among the working-age individuals, with its pathogenesis poorly understood. This study aimed to elucidate the role of ferroptosis in HMC development as well as the underlying mechanisms. In HMC lens epithelia, levels of Fe2+ and lipid peroxidation were found elevated, with increased vulnerability towards ferroptosis as revealed by transmission electron microscopy. Mechanistically, RNA sequencing of HMC lens epithelial samples identified up-regulated expression of discoidin domain receptor tyrosine kinase 2 (DDR2) as a key factor, which could enhance ferroptosis sensitivity via the Src-Hippo pathway. Specifically, DDR2 interacted with Src kinase, leading to the nuclear translocation of homologous transcriptional regulators (yes-associated protein 1 [YAP1] and WW domain containing transcription regulator 1 [WWTR1]) of the Hippo pathway, which altered the expression level of ferroptosis-related genes. Notably, highly myopic eyes of mice exhibited higher sensitivity to RSL3, a ferroptosis inducer, manifested as more severe nuclear lens opacities both in vitro and in vivo compared with the contralateral control eyes, which could be alleviated by inhibitors of either ferroptosis or DDR2. Altogether, these findings highlighted the role of DDR2 in mediating ferroptosis in HMC formation, providing a novel insight for therapeutic interventions.