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.