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Jordan A. Greco, Nicole L. Wagner, Ralph J Jensen, Robert R. Birge; Stimulation of Retinal Ganglion Cells Using an Ion-Mediated, Protein-Based Retinal Implant. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4184.
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© ARVO (1962-2015); The Authors (2016-present)
Protein-based subretinal implants offer a new approach to restoring vision for patients blinded by age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Ex vivo extracellular recording experiments with P23H transgenic rats are employed to demonstrate the ability of an ion-mediated, protein-based prosthetic to stimulate the bipolar and ganglion cells of a degenerated retina.
Retinal implant constructs, comprised of an ion permeable membrane and alternating layers of bacteriorhodopsin (BR) and a polycation binder, are manufactured using layer-by-layer electrostatic adsorption. Upon the absorption of light, the BR layers generate a unidirectional proton gradient that activates acid-sensing ion channels (ASICs) present in the outer membrane of bipolar and ganglion cells. The retinal implants are placed in a subretinal position relative to the excised retina of P23H transgenic rats, and a pulsed LED system is used to generate precise pulses at a wavelength that selectively activates BR. Extracellular recording, using both a single electrode and multielectrode array, is carried out to validate the ion-mediated mechanism of action and to investigate the spatial sensitivity of the retinal prosthetic.
Studies using extracellular recording of retinal ganglion cells in excised P23H rat retinas indicate that that our subretinal implant is capable of stimulating the retinal tissue via a directional proton gradient. The activation efficiency of the protein-based prosthetic increases with the increasing intensity of incident red light (~640 nm). The experiments suggest that the implant can stimulate the retina using light intensities that are comparable to indoor ambient light (~7.2 mW/cm2), and also demonstrate that the temporal resolution of the prosthetic is similar to physiological latency of activation (~100 ms). Moreover, a multielectrode array is used to show that we can limit activation to a 200-μm pixel diameter.
The preliminary results suggest that a BR-based retinal implant can stimulate the remaining neural circuitry of P23H retinas, demonstrating the potential efficacy in the treatment for AMD and RP.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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