Millions worldwide are afflicted by cataract (Khairallah et al., 2015; Lee and Afshari, 2017). The etiology of cataracts is very complex, and includes nutritional, metabolic, environmental, and genetic factors (Zhu et al., 2017). Solar ultraviolet (UV) radiation is the primary risk factor for cataractous lenses (Delcourt et al., 2014; Löfgren, 2017). Ultraviolet B (UVB) (280–315 nm) rays may severely injury lenses in various animals (Andley et al., 1994; Kleiman et al., 1990; Mesa and Bassnett, 2013) because the wavelengths that are most harmful to lenses are located around 300 nm (Ivanov et al., 2018). Our previous study and other research revealed that UVB irradiation contributed to the initiation and development of cataracts (Dave et al., 2019; Guo et al., 2022; Zhang et al., 2012).

Glutaredoxin 2 (Grx2) is a member of the glutaredoxin family of thiol-disulfide oxidoreductases required to maintain cellular redox homeostasis (Fernandes and Holmgren, 2004). Grx2 confers protection against oxidative pathologies (Kanaan et al., 2018; Lepka et al., 2017; Romero et al., 2017). Deletion of the Grx2 gene expedites cataract formation (Wu et al., 2014). Although Grx2 plays an important role in defending the oxidative damage caused by UVB radiation as our previous studies documented (Guo et al., 2022), its mechanism is still not fully understood.

UVB radiation can induce crystallin aggregation, oxidative damage and lipid peroxidation in cells (Costanzo et al., 1995; Hott and Borkman, 1993; Ivanov et al., 2018; Katsuyama et al., 2021; Moison and Beijersbergen van Henegouwen, 2002). Previous studies demonstrated that UVB-induced lens epithelial cell (LEC) injury leads to apoptosis (Ji et al., 2015; Jia et al., 2018; Li and Spector, 1996) or pyroptosis (Sun et al., 2020), thus resulting in the formation of cataractous lenses. In addition, ferroptosis is a new type of cell death which is different from apoptosis and pyroptosis.

Ferroptosis—newly programmed iron-dependent cell death characterized by lipid peroxidation and excessive oxidative stress (Stockwell, 2022)—plays an important role in neurodegenerative diseases, tumors, myocardial injury and other diseases (Jiang et al., 2021; Stockwell et al., 2020). Much evidence has indicated that iron is a risk for cataract development because of its ability to catalyze free radical formation (Loh et al., 2009). Lipid peroxidation is a pathogenic factor in cataractogenesis (Borchman, 2021; Huang et al., 2005; Kreuzer et al., 2020). Moreover, LECs are highly susceptible to ferroptosis (Wei et al., 2021). Ferroptosis is a crucial process involved in the formation of cataracts (Tang et al., 2024; Wang et al., 2023; Zhang et al., 2024). The focus of this study is whether Grx2 protects the lens from UVB damage by resisting ferroptosis.

In this study, we investigated that Grx2 exerts a protective role in UVB irradiation as a ferroptosis inhibitor. By detecting the characteristics, we have further confirmed that UVB exposure induces ferroptosis in lens epithelial cells. Additionally, Grx2 plays strengthens resistance to ferroptosis induced by UVB irradiation through maintaining HLECs cellular GSH/GSSG homeostasis. This study brings new understanding of how Grx2 protects against cataracts caused by UVB.