New model of complete retinal degeneration: A good tool for therapeutic essays?

Abstract

AbstractPurpose: To characterize a mouse model of complete blindness after induction of retinal degeneration based on the degenerative capacity of NaIO3 on cell photoreceptors, rods and cones, and to test the effect of new pharmacological tools.Methods: Two doses of NaIO3 (40 mg/kg and 60 mg/kg) were intraperitoneally injected into a series of C57BL/6J mice with a mutation in the Opn4−/− gene. The effect of NaIO3 on the retina was assessed at 7, 14, 21 and 28 days after the injection by means of visual behavioural test, electroretinogram (ERG) recordings and immunohistochemical staining. To further assert the model's effectiveness, new optopharmacological agents were tested on the developed model, followed by visual testing.Results: Both doses of the degenerative agent induced a gradual reduction of the visual capacities of the animals. The different components of the ERG waves showed a marked decrease in their amplitude throughout the 28 days of the experiment, with the 60 mg/kg dose provoking a more pronounced functional loss. Similar results were observed in the behavioural tests, in which the animals' visual sensitivity, visual acuity, photomotor capacity were highly decreased. Same tests were performed under the effect of new optopharmacological therapies. Our results demonstrate not only the model's effectiveness, but also the usefulness of the new therapy for vision recover.Conclusions: NaIO3 induced murine model of retinal degeneration seems to be a good model for testing new pharmacological approaches to retinal diseases. Assessment of retinal function by electrophysiological tests, visual animal behaviour and retinal histology seem to be basic and reliable techniques for the evaluation of drug effect on this new animal model.