Establishment of retinal degeneration model in rat and monkey by intravitreal injection of sodium iodate.

BACKGROUND: Animal models play critical roles in studying etiology and therapy of retinal degeneration (RD).

OBJECTIVE: To establish a RD model in monkey without severe systemic side-effects.

METHODS: Cynomolgus monkeys and Sprague-Dawley rats were treated with intravenous and intravitreal sodium iodate (SI). The ERG, FFA, OCT and retinal morphology were examined to evaluate the retinal function and structure. ARPE19 cells were treated with SI for cell viability and morphology examinations. GSH was used to the SI-treated culture cells and rats for mechanistic study.

RESULTS: Intravenous SI failed to induce retinal degeneration in monkeys due to its lethal toxicity and spontaneous recovery of the visual function. Intravitreal injection of SI induced very faster and violent retina damages in monkeys and rats. Different dosages of SI were tested in both rats and monkeys and a proper SI dosage for the model was calculated. Glutathione partially rescued the oxidation-damage in SI-treated retinas, but not through neutralizing SI. Combination of a proper dosage of intravitreal SI and intravenous GSH could generate a moderate sub-acute degeneration in retina.

CONCLUSIONS: Retinal degeneration model could be established in cynomolgus monkey by intravitreal injection of SI. Its key advantages are that the lethal SI side-effects can be avoid, and the structural and functional changes are closer to those in the patients with retinal degeneration, except it develops too fast and more severe. A proper dosage of SI plus systemic GSH generates a delayed and moderate degeneration in retina. Such a prolonged therapeutic window provides a tool for development of new therapies like gene or stem cell-based therapy for retinal degeneration.