Background: Animal models play critical roles in studies of the etiology and
therapy of retinal degeneration (RD).
Objective: To establish an RD model without severe systemic side effects in monkeys.
Methods: Cynomolgus monkeys and Sprague-Dawley rats were treated with
intravenous and intravitreal sodium iodate (SI). Electroretinographic (ERG) recording,
fluorescein fundus angiography (FFA), optical coherence tomography (OCT) and a
retinal morphology examination were conducted to evaluate retinal function and
structure. ARPE-19 cells were treated with SI to assess cell viability and morphology.
Glutathione (GSH) was administered to SI-treated cultured cells and rats for mechanistic
Results: Intravenous SI failed to induce RD in monkeys due to its lethal toxicity and the
spontaneous recovery of visual function. However, intravitreal SI injection induced very
rapid and severe retinal damage in both monkeys and rats. Different doses of SI were
tested in both rats and monkeys, and the SI dose appropriate for the model was
calculated. GSH partially rescued oxidative damage to SI-treated retinas. A combination
of the appropriate dose of intravitreal SI and intravenous GSH generated moderate
Conclusions: An RD model was established in cynomolgus monkeys by intravitreal SI
injection. The key advantages of this model are that lethal SI side effects can be avoided
and that the structural and functional changes are similar to those in patients with RD,
although the development of RD in the model is too rapid and more severe. An
appropriate dose of SI plus systemic GSH generates delayed and moderate RD; this
prolonged therapeutic window allows the development of new therapies, such as gene
or stem cell-based therapy, for RD.