GPx4 reduces laser‐induced choroidal neovascularization by inhibiting ferroptosis

Abstract Purpose: To investigate the protective effects of glutathione peroxidase 4 (GPx4) in laser‐Induced age‐related macular degeneration (AMD) animal model. Methods: In this study, Norway brown rats were used to establish a laser‐induced AMD model. To investigate the protective role of GPx4, rats received laser photocoagulation and intravitreal injection of GPx4 (25 μg/eye) or PBS on the same day. The size and vascular leakage of choroidal neovascularization (CNV) were measured on 7 and 14 days after lasing by using OCT and FA. Immunohistochemical staining of the choroidal flat mounts with CD31 were used to assess angiogenesis. Results: Compared with PBS group, intravitreal injection of GPx4 decreased the CNV size of 0.083 ± 0.121, P = 0.07 on day 7 and 0.11 ± 0.135 ( p < 0.05) on day 14. By leakage grading, the CNV lesion with pathologically significant leakage (grade 2a and 2b) was reduced in GPx4 group (2%) and increased in PBS group (25.6%) from day 7 to day 14. The immunostaining with CD31 showed smaller lesions in GPx4 group than PBS group. Conclusions: This study showed that GPx4 inhibited CNV formation and providing a novel molecular target against ferroptosis for wet AMD treatment.