Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.

Abstract

Purpose: Geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD), has limited treatment options. This study introduces a novel mouse model featuring an expanding GA patch that can be used to test mechanisms and therapeutics.

Methods: C57Bl/6J male mice (n = 96) aged 9-10 weeks received an intraperitoneal (IP) injection of 20 mg/kg sodium iodate (NaIO3). In vivo confocal scanning laser ophthalmoscope (cSLO) and optical coherence tomography imaging were done at one, four, eight, and 16 weeks after injection, with GA area measurements taken at weeks 8 and 16. Mice were euthanized on weeks 8 and 16 for histological analysis.

Results: Administration of 20 mg/kg intraperitoneal NaIO3 caused variable damage levels. Approximately 22% of cases showed damage (speckled autofluorescence) covering 35% to 90% of the 102° field of view cSLO image at one week after injection. These mice developed an expanding patch of GA by week 8, with a mean 1.45-fold increase in area by week 16. This region showed complete photoreceptor and retinal pigment epithelium loss and complement activation at the atrophy edge, whereas the inner retina remained undamaged. Mice with less damage (48% of cases) only developed incomplete outer retinal degeneration, and mice with more damage (30% of cases) had too much GA for measurable expansion.

Conclusions: Although expanding GA formed in only 22% of mice, the model's simplicity and predictability for GA development via one-week post-injection imaging make it suitable for GA therapeutic experimentation.

Translational relevance: This murine model provides a valuable tool for testing GA therapies, mirroring clinical endpoints relevant to human trials.