Purpose: Age-related cataract (ARC) is one of the leading causes of blindness and visual impairment globally. The aim of this study was to explore the role of Notch 3 in ARC as well as the mechanisms underlying Notch 3 in ARC. Methods: An in vitro model was established to mimick the microenvironment of ARC, the lens epithelial cell line (LEC) B3 were treated with hydrogen peroxide (H 2 O 2 ) once they reached approximately 80% confluence. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of LEC B3. The mRNA of Notch 3 was detected via RNA extraction and quantitative real-time PCR (RT-qPCR). The protein level of Notch 3 was measured by western blot. Results: The mRNA and protein expression of Notch 3 were evidently down-regulated in H 2 O 2 -inducted LEC B3. Overexpression of Notch 3 increased the proliferation and suppressed the apoptosis of H 2 O 2 -inducted LECs B3. The elevated level of Notch 3 decreased the reactive oxygen species (ROS) fluorescence intensity and decreased Fe 2+ and total Fe levels. In addition, Notch 3 up-regulation increased the levels of ferroptosis-related proteins GPX4 and SLC7A11. Notch 3 overexpression decreased the protein levels of p-PI3K, and p-AKT in H 2 O 2 -treated LECs B3. PI3K/AKT pathway inhibitor reversed the role effect of Notch 3 overexpression on the proliferation, apoptosis, and ferroptosis of LECs cells in ARC model. Conclusion: The present study identified that Notch 3 regulates ferroptosis of LECs B3 in ARC by PI3K/AKT pathway, which might offer a novel biomarker for the future investigation of the target of ARC.
Zhang et al. (Sat,) studied this question.