Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy
De Silva SR., Barnard AR., Hughes S., Tam SKE., Martin C., Singh MS., Barnea-Cramer AO., McClements ME., During MJ., Peirson SN., Hankins MW., MacLaren RE.
Significance Inherited retinal degenerations may result in blindness due to a progressive loss of photoreceptor cells. We assess subretinal delivery of human melanopsin using an adeno-associated viral vector to remaining retinal cells in a model of end-stage retinal degeneration. Human melanopsin, being already present in the eye, is unlikely to generate an immune response when introduced via gene therapy. Furthermore, this method of delivery has been proven to be safe in clinical trials and may be more effective at delivering vector in primates than the alternative method of intravitreal injection. We demonstrate long-term vector expression and restoration of visual function, indicating that this therapy could be stable and efficacious in the treatment of patients with end-stage retinal degenerations.