NaIO3-induced RPE toxicity leads to chorioretinal atrophy, scleral remodeling, and myopic axial elongation in mice

Pathologic myopia, a vision-threatening subtype of myopia, is characterized by axial elongation accompanied by chorioretinal atrophy and scleral remodeling. While lens-induced and form-deprivation myopia models have elucidated the role of visual input in ocular growth, the contribution of retinal pigment epithelium (RPE) and choriocapillaris (CC) damages remains incompletely understood. Here, we employed a sodium iodate (NaIO₃) model—traditionally used in age-related macular degeneration research—to investigate whether the damage to the RPE and CC can induce changes in the sclera and axial length. We demonstrate that systemic NaIO₃ exposure induced widespread RPE and CC degeneration, retinal thinning, and chorioretinal atrophy, all of which were partially rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1) in mice. These degenerative changes correlated with a significant myopic shift (∼15 D) and axial elongation (∼0.3 mm), alongside scleral thinning, decreased COL1A1 expression, and reduced collagen fibril diameter—hallmarks of scleral extracellular matrix remodeling. Fer-1 treatment attenuated both the anatomical and molecular features of myopia, supporting a causal role of lipid peroxidation in this process. Our findings demonstrate that lipid peroxidation-associated RPE and CC damage can trigger scleral remodeling and axial elongation independent of visual input, providing a novel mechanistic insight into ocular growth regulation. The NaIO₃ model may therefore serve as a unique and reproducible platform for studying chorioretinal degeneration-driven myopia and evaluating lipid peroxidation-targeting therapies.