Dog models for blinding inherited retinal dystrophies

Abstract

Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.

FIG. 1.

RPE65 gene therapy in a dog. (A) Fundus photographs of the treated eye of an Rpe65-mutant dog preinjection, immediately postinjection, and 6 months postinjection. Note the large region of retinal detachment resulting from the subretinal administration of the viral vector. (B) Electroretinographic outcome. Part of a dark-adapted intensity response series and 33 Hz light-adapted cone flicker response is shown from the treated eye and control eye of an Rpe65-mutant dog.^, AAV2/2hRPE65p.hRPE65 vector had been delivered by subretinal injection 4 months previously in the treated eye. The ERG tracings show that there is excellent restoration of both rod- and cone-mediated ERG responses. The magnitude of ERG amplitudes approaches those of normal dogs. (Dark-adapted intensities from top to bottom: 0.0016, 0.0099, 0.064, and 0.399 cdS/m². Light-adapted 33 Hz cone flicker intensity 2.5 cdS/m² superimposed on a rod suppressing 30 cd/m² white-background light). ERG, electroretinogram.