Gold nanoparticle Neurosensory Epiretinal Implant to Treat Photoreceptor Vision Loss

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PROJECT ABSTRACT The retinal degenerative and dystrophic pathologies are major causes of blindness through the lifespan. There is thus a critical need to find novel therapeutic devices which can address this broad group of devastating diseases. Gold-nanoparticle neurosensory epiretinal stimulator (GNES) is one such device, an implant without external power generation for stimulation of remaining retinal ganglion cells to restore vision. Gold nanoparticles placed on a dielectric layer have the potency to generate voltage on exposure to certain wavelengths. Intriguingly, these phenomena can be exploited to use them as photoreceptors. The long-term goal is to address the need for biocompatible neurosensory devices, modifying the design for high resolution and long lasting GNES for patients with retinal dystrophy and degenerations. The proposed research will assess an autonomous GNES that can passively mix the effect of optical signals and directly excite remaining retinal ganglion cells. The rationale for this research is that gold- nanoparticles are voltage generating particles without the need for image processing, power source or extensive surgery for the intraocular and extraocular component. The objective in this application is to modify GNES as a retinal ganglion cell stimulator. The overall hypothesis is that gold nanoparticles on a dielectric platform can serve as a stand-alone neurostimulator that excites RGCs and are biocompatible with lasting excitatory capability. The hypothesis will be tested via two specific aims: 1. Assess the excitation of RGCs ex vivo using GNES device. GNES excitation will be assessed using two methods. First with multielectrode array (MEA) with human stem cell induced RGCs growth over GNES. In addition, we will use Genetically Encoded Calcium Indicator (GECI) mice crossed with rd1 mice which lack photoreceptors. We will test the GNES response to different wavelengths and spatial resolution. 2. Determine the feasibility of refined GNES with Light Shutter Valve (LSV). One of the concerns in electrical stimulation is overheating the system or neurotoxic effect of constant stimulation. The effect of LSV on RGC survival will be tested with prolonged retinal explants. The morphology and functional assay of RGCs will be tested after prolonged culture or exposure to stimulation. This work is innovative, as it is the first epiretinal implantable device with standalone capability and capacity to regulate the light. The work is highly significant because it will define GNES and LSV as a new tool to address the clinical challenge in treating patients with photoreceptor loss, leading to development of new ways to restore vision.