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Activated ferroptosis caused hyaloid vascular abnormalities in aldh3b1-/- and in 2-HD treated zebrafish.A Graphical view of the occurrence and regulatory pathways involved in ferroptosis. Created in BioRender. Bennewitz, K. (2026) https://BioRender.com/p96mk4e. B, Caldh3b1 deficiency and 2-HD treatment increased lipid peroxidation as determined by increased MDA (malondialdehyde) formation in zebrafish larvae (B, n = 4 for each group) and eye (C) (n = 4/4). Daldh3b1 deficiency and 2-HD treatment increased the percentage of Fe2+ /Fe3+ in larvae (n = 4 for each group). E, F Reduced gpx4 and fsp1 mRNA expression caused by aldh3b1 deficiency and 2-HD treatment (n = 6 for each group). G Immunoblot analysis revealed decreased Fsp1 and Gpx4 proteins in aldh3b1-/- and 2-HD treated aldh3b1+/+larvae (n = 3 for each group). H–J Reduced fsp1, gpx4 and nrf2a mRNA levels in eyes from adult aldh3b1-/- zebrafish (n = 6/6). Kaldh3b1 deficiency decreased Fsp1 and Gpx4 proteins in the zebrafish eye (54 = 4/4). L, M 10 µmol iFSP1 significantly increased hyaloid sprouts (L) and branchpoints (M) in aldh3b1+/+ larvae (n = 13 for each concentration). N, Oaldh3b1-/- and 2-HD induced hyaloid vascular alterations can be rescued by Ferrostatin-1 (n = 14 for each group). MDA, malondialdehyde; GPX4, glutathione peroxidase 4; FSP1, ferroptosis suppressor protein 1; NRF, nuclear factor erythroid 2-related factor; Ferr-1, ferrostatin-1. Statistical analysis was performed using two-tailed Student’s t test for panels (C, H–K) and one-way ANOVA for (B, D–G and L–O). The bars indicate mean ± SD values. Source data are provided as a Source Data file.
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