Regulated cell death pathways in the sodium iodate model: Insights and implications for AMD

The sodium iodate (NaIO3) model of increased oxidative stress recapitulates dry AMD features such as patchy RPE loss, secondary photoreceptors, and underlying choriocapillaris death, allowing longitudinal evaluation of the retinal structure. Due to the time- and dose-dependent degeneration observed in diverse animal models, this preclinical model has become one of the most studied models. The events leading to RPE cell death post- NaIO3 injection have been extensively studied, and here we have reviewed different modalities of cell death, including apoptosis, necroptosis, ferroptosis, and pyroptosis with a particular focus on findings associated with in vivo and in vitro NaIO3 studies on RPE cell death. Because the fundamental cause of vision loss in patients with dry AMD is the death of these same cells affected by NaIO3, studies using NaIO3 can provide valuable insights into RPE and photoreceptor cell death mechanisms and can help understand mechanisms behind RPE degeneration in AMD.