Abstract
Recent gene therapy progress has raised the possibility that vision loss caused by inherited retinal degeneration can be slowed or prevented. Unfortunately, patients are not usually diagnosed until enough degeneration has occurred that the deterioration in vision is noticeable. Therefore, effective gene therapy must halt degeneration to stabilize and preserve any remaining vision. Gene therapy methods currently in human clinical trials rely on subretinal or intravitreal injections of adeno-associated virus to deliver the therapeutic gene. To date, long-term results in patients treated with subretinal injections for Leber congenital amaurosis have been mixed. Proposed limitations include variability in the gene delivery method and a possible point of no return, at which treatment would be ineffective. In this issue of the JCI, Koch et al. describe a well-controlled and precise mouse model for testing the ability of gene therapy to halt the progress of degeneration. Instead of viral-mediated therapeutic gene delivery, the authors induced expression of an integrated transgene at specific times during the course of photoreceptor degeneration. In Pde6b-deficient retina, this strategy halted degeneration, even when more than 70% of photoreceptors had already degenerated. The results of this study demonstrate that retinal degeneration can be stopped, even at late stages of disease.