Grant: CIHR Fellowship

Despite dozens of clinical trials (and countless animal trials) to regenerate the retina with stem cell transplants, none have solved the challenge successfully. This is because the retina has many layers, and all layers are necessary in order to permanently restore vision in patients with advanced retinal degeneration - ~1 million patients in Canada and >50 million worldwide. This results in a staggering amount of suffering and considerable global economic burden of 1/3rd of a trillion dollars (USD) annually for age-related macular degeneration (AMD) alone (not including the millions of patients that suffer from advanced, diabetes-related or inherited, retinal degeneration). Current stem-cell suspension transplants can only replace a single retinal layer. Retinal pigment epithelium (RPE) transplants can delay further degeneration, but they cannot replace dead photoreceptors. Photoreceptor transplants indeed restore vision, but only briefly since the diseased RPE cannot maintain the new photoreceptor graft. Current scaffold- or sheet-based transplants can be multi-layered. However, they provide limited retinal coverage, result in higher levels of surgical trauma than suspension injection, form inappropriate graft structure, and cause additional cell death - in many cases destroying the layer they were designed to regenerate. Given this, there is considerable need for simple, atraumatic replacement of multiple retinal layers. Here, we propose to continue development of new technology that organizes subretinal graft (including RPE and photoreceptors) into correct orientation and layering with wide coverage. This therapeutic is administered using standard outpatient surgical techniques and infrastructure. We have attained dual-graft stratification in: in vitro, pig ex vivo, and rabbit in vivo models. The next critical step towards the clinic is larger-scale animal trials assessing vision benefit.