Retinal degenerative diseases lead to blindness due to loss of the "image capturing" photoreceptor layer, while neurons in the "image processing" inner retinal layers are preserved to a large extent. Electronic retinal prostheses seek to restor sight by electrical pattern stimulation of surviving neurons. Very encouraging clinical results with the first retinal prostheses have been recently demonstrated. However, current implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We developed a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel directly convert pulsed near-infrared (NIR) images projected from video goggles into local electric currents to stimulate neurons. This system offers multiple advantages over other designs: due to wireless activation of the pixels in the implant the system is scalable to thousands of electrodes;it maintains the natural link between eye movements and image perception;the implantation is greatly simplified and modular design of the implant allows expanding the visual field by tiling;pillar electrodes allow cellular-scale proximity to the targe neurons. Such a versatile system could be used to address the divergent needs of patients with various forms of retinal degeneration. We have manufactured and tested the first generation of the implants. Photovoltaic arrays show long-term biocompatibility, and provide safe retinal stimulation upon illumination with NIR pulses in-vitro and in-vivo. We now seek to produce the implants designed for highest resolution and lowest stimulation thresholds, and protected by inert and biocompatible coatings for long-term implantations. To achieve these goals we will assess visual acuity and contrast sensitivity obtained with subretinal photovoltaic implants of different designs in-vitro and in-vivo in animals with normal and degenerate retinas. This project brings together a unique combination of engineers, neuroscientists and ophthalmologists to complete the development and evaluation of a high-resolution retinal prosthetic system designed specifically for achieving the functional levels of vision.

Public Health Relevance

Retinal degenerative diseases lead to blindness due to loss of the image capturing photoreceptor layer, while neurons in the image processing inner retinal layers are preserved to a large extent. We developed a photovoltaic subretinal prosthesis, in which photodiodes in each pixel directly convert pulsed near- infrared images projected from video goggles into local electric currents and stimulate neurons. This system is scalable to thousands of pixels, is easily implantable, and maintains the natural link between eye movements and image perception. This innovative design has the potential to addresses the divergent needs of patients with various forms of retinal degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY018608-05
Application #
8477527
Study Section
Special Emphasis Panel (ZRG1-ETTN-B (51))
Program Officer
Shen, Grace L
Project Start
2009-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$1,133,737
Indirect Cost
$323,272
Name
Stanford University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Lorach, Henri; Goetz, Georges; Mandel, Yossi et al. (2015) Performance of photovoltaic arrays in-vivo and characteristics of prosthetic vision in animals with retinal degeneration. Vision Res 111:142-8
Boinagrov, David; Pangratz-Fuehrer, Susanne; Goetz, Georges et al. (2014) Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes. J Neural Eng 11:026008
Scott, Patrick A; Fernandez de Castro, Juan P; Kaplan, Henry J et al. (2014) A Pro23His mutation alters prenatal rod photoreceptor morphology in a transgenic swine model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 55:2452-9
Fransen, James W; Pangeni, Gobinda; Pardue, Machelle T et al. (2014) Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo. J Neural Eng 11:046012
Boinagrov, David; Palanker, Daniel (2014) Reply to Rattay. J Neurophysiol 112:2666
Fernandez de Castro, Juan P; Scott, Patrick A; Fransen, James W et al. (2014) Cone photoreceptors develop normally in the absence of functional rod photoreceptors in a transgenic swine model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 55:2460-8
Goetz, G A; Mandel, Y; Manivanh, R et al. (2013) Holographic display system for restoration of sight to the blind. J Neural Eng 10:056021
Sher, Alexander; Jones, Bryan W; Huie, Philip et al. (2013) Restoration of retinal structure and function after selective photocoagulation. J Neurosci 33:6800-8
Mandel, Yossi; Goetz, Georges; Lavinsky, Daniel et al. (2013) Cortical responses elicited by photovoltaic subretinal prostheses exhibit similarities to visually evoked potentials. Nat Commun 4:1980
Ross, Jason W; Fernandez de Castro, Juan P; Zhao, Jianguo et al. (2012) Generation of an inbred miniature pig model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 53:501-7

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