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    218—Nanotools for Neuroscience

    Sunday, November 10, 2013, 1:00 pm - 3:45 pm

    218.01: High density optoelectronic nanowire array selective stimulation of the neural retina: Comparison with other neural stimulation technologies

    Location: 7B

    *G. A. SILVA;
    Bioengineering, UCSD, LA JOLLA, CA

    Abstract Body: Retinal prosthesis, which have been proposed as a potential treatment for degenerative retinal disorders that lead to vision loss and blindness, offer an alternative engineered approach with a number of advantages over biological approaches for treating these disorders. However, existing retinal prosthesis continue to experience serious engineering limitations that prevent them from reproducing functional vision. In contrast, we are developing a nanoengineered retinal prosthesis made up of ultra-high density arrays of light sensitive ππnanowires that overcome these limitations, resulting in a device that reproduces biological resolution and exceeds the spectral properties of the human retina, while at the same time requiring very low power to drive it. Here, we will discuss our newest results related to the electrophysiology of stimulated ganglion cells in the context of and comparing this technology to other neural stimulation technologies.

    Lay Language Summary: Our team is developing and testing a novel neural stimulation nanotechnology consisting of regular arrays of light sensitive optoelectronic nanowires. Each nanowire is incredibly thin, on the order of 100 times thinner than a human hair. Arrays of these nanowires are being designed to be surgically implanted into the eye to electrically stimulate the remaining neural retina in the back of the eye of blind patients with degenerative retinal disorders such Age Related Macular Degeneration or Retinitis Pigmentosa. The potential retinal neural stimulation properties of these devices are singularly unique. Their stimulation density is extremely high, and has the potential to exceed the native resolution of the biological human retina (i.e. the normal density of light sensitive photoreceptor neurons) by a factor of ten. They can potentially exceed the density of existing microtechnology retinal prosthesis by 10,000 to 100,00 times. They have a very high light capturing ability (quantum capture), approaching some of the best CCD cameras that exist. And they can respond to very broad wavelengths of light, far exceeding the normal range of the human visual spectrum. Although the research is in early stages and there are many engineering and neurobiological challenges to overcome before we get to a clinically ready retinal prosthesis device, our accumulating data are very encouraging.
    Our approach is the first such technology engineered at the nanoscale that has the potential to achieve (and even exceed) biological resolution in a retinal prosthetic device. We are the first group to show that an optoelectronic nanowire technology can successfully achieve phototransduction stimulation of retinal tissue. To test the devices, we stimulate the nanowire arrays with light that the retina cannot see in various animal models, and then record the resultant electrophysiological activity of retinal ganglion cells in the retina itself or activity in visual cortex responding to electrical stimulation of the retina by the devices. Retinal ganglion cells are the neurons that project to the higher visual centers in the brain.
    This work is an example of emerging nanotechnologies intended for interfacing, stimulating, and recording from the central nervous system. Existing microtechnology retinal prosthesis devices are subject to a number of limitations in their ability to reach appropriate electrode densities and stimulation resolutions. These are fundamental engineering limitations that will be difficult to overcome. The jump from micro to nano, or three orders of magnitude in scale, results in fundamental differences in physical and chemical properties that are unique to the nanoengineered device not shared by the bulk materials from which they are composed. This allows nanotechnologies to interact with neural cells and tissues completely differently than microtechnologies. In our technology the shape of the nanowires at the nanoscale affects how they capture light and convert it into an electrical output capable of stimulating retinal neurons. On-going work is focused on improving the sensitivity and electrical output of the devices while minimizing power requirements, and on establishing design and engineering criteria for an initial clinical device.
    Retinal degenerations occur when photoreceptor neurons, which normally transduce incoming light into a neurochemical signal in the retina, die away. The neural retina is actually a part of the brain and central nervous system that extends out into the eye. Attempts to treat these disorders by slowing down the rate of degeneration and reversing the resultant loss of vision have included genetic, pharmacological, surgical, and cellular interventions. While each of these treatments offers promise, they also face numerous challenges that have kept high impact therapies from reaching the clinic. In contrast, retinal prostheses offer a neural engineering and technology focused solution to the problem of restoring vision to these patients.