Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis

• DOI: 10.1016/j.redox.2023.102890
• Publication Date: 2023-09-17T15:30:26Z
• Authors: Kazuhisa Yamada; Akira Tazaki; Nanako Ushio-Wata...; Yoshihiko Usui; Atsunobu Takeda; Masaaki Matsunaga; Ayana Suzumura; Hideyuki Shimizu; Hao Zheng; Nanang R. Ariefta; Masahiro Yamamoto; Hideaki Hara; Hiroshi Goto; Koh-Hei Sonoda; Koji M. Nishiguchi; Masashi Kato; Yoshifumi Nishikawa; Shinya Toyokuni; Hiroki Kaneko
• Keywords: Toxoplasmosis

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), severe sight-threatening disease. Nevertheless, diagnosis OT based on findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, efficacy OT-targeted treatment limited; thus, additional measures for treatments are needed. Here, we first time report significantly reduced iron concentration in vitreous humor (VH) human patients infected OT. To obtain further insights into molecular mechanisms, established mouse model T. gondii infection, intravitreally injected tracer 57Fe, was accumulated neurosensory retina. gondii-infected eyes showed increased lipid peroxidation, reduction glutathione peroxidase-4 expression mitochondrial deformity photoreceptor cristae loss. These findings strongly suggest involvement ferroptotic process In addition, deferiprone, an FDA-approved chelator, uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. conclusion, levels VH could serve diagnostic markers chelators potential