Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy

Geographic atrophy (GA) is characterized by the loss of choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors and is an advanced form of age-related macular degeneration (AMD)-a leading cause of central vision loss in the elderly. The development of effective treatments has been hindered by the lack of reliable animal models that recapitulate the structural, functional, and molecular hallmarks of GA. In this study, we established and extensively characterized a sodium iodate (NaIO₃)-induced model of GA in pigmented Long Evans rats using a comprehensive set of in vivo and histological techniques. NaIO₃ was administered intraperitoneally at 80 mg/kg to induce bilateral retinal degeneration. Morphological, functional, and ultrastructural changes were evaluated using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG), light and electron microscopy, and immunohistochemistry at pre-dose and 3, 7, and 14 days post-injection. The model exhibited typical GA features including choriocapillaris loss, RPE degeneration, photoreceptor death, Bruch's membrane remodeling, and mitochondrial damage. Complement activation (C3, C5b-9) and immune cell infiltration (Iba1, CD68) were observed, along with gliosis and RPE65 loss. ERG analysis revealed profound and persistent functional deficits. These findings demonstrate that the NaIO₃ rat model robustly mimics the key pathological events in GA, particularly at 7 days post-injection, making it a suitable model for preclinical evaluation of therapeutic interventions targeting choriocapillaris and RPE protection.