Degenerative diseases of the outer retina such as Retinitis Pigmentosa (RP) and Age-related Macular Degeneration (AMD) are the main underlying causes of blindness. In these diseases “the image capturing layer” of the retina, the photoreceptors, degenerate whereas the remaining neural cells that process the information (bipolar and horizontal cells) and relay it to the brain (the ganglion cells) are left relatively intact. Most current strategies for vision restoration rely on the electrical stimulation of these remaining cells. While these approaches offer promising improvements in the life quality of the transplanted patients, the obtained visual acuity is far from the desired normal visual acuity. Alternative approaches rely on novel advancements in stem cell research and are based on cellular replacement therapy. In this approach photoreceptors are differentiated from either stem cells (ES) or induced pluripotent stem cells (iPSC) and are transplanted in the subretinal space to replace the degenerate photoreceptors. Notwithstanding the demonstration of vision restoration using this approach in several animal models, it is still limited by the need for obtaining fully mature photoreceptors and the proper integration of the transplanted cells with the host retina.
To overcome these limitations, our group pursued a novel approach, which we term the hybrid retina (HRI), relying on the incorporation of differentiated photoreceptors with a high-density electrode implant and its implantation in the subretinal space. We hypothesized that the transplanted cells will properly integrate with the host retina and that their electrical stimulation through the electrodes on which they are seeded will result in a retinal prosthesis providing unprecedented visual acuity. Throughout the project we have made great strides towards the realization of this challenging approach. Whereby we have successfully fabricated a high-density electrode array device at the bottom of each well is a gold electrode centrally located for neuronal electrical stimulation. Moreover, we have demonstrated the integration of this device incorporated with photoreceptor precursors with the host retina of a blind rat model. Furthermore, we have identified optimal electrode surface treatments which enhance the cell-electrode coupling, thus reducing activation thresholds and increasing the spatial resolution of the obtained prosthetic vision. Furthermore, we identified small molecules that putatively improve the integration of the transplanted cells with the host retina and promote synaptogenesis. Finally, using an in-vitro prototype of the implant we demonstrated the significant reduction of activation thresholds of cells seeded on the device, compared with cells seeded on planar flat electrodes.
The Hybrid Retinal Implant, thus, introduces a promising solution to a large population of AMD patients who would only benefit from a high-resolution vision restoration, as their peripheral vision is largely still intact.
