Retinal prosthetic strategy with the capacity to restore normal vision

Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2012; 109(37):15012-7. DOI: 10.1073/pnas.1207035109
Source: PubMed


Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20-25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their best hope is through prosthetic devices [reviewed in Chader et al. (2009) Prog Brain Res 175:317-332]. Current prosthetics, however, are still very limited in the vision that they provide: for example, they allow for perception of spots of light and high-contrast edges, but not natural images. Efforts to improve prosthetic capabilities have focused largely on increasing the resolution of the device's stimulators (either electrodes or optogenetic transducers). Here, we show that a second factor is also critical: driving the stimulators with the retina's neural code. Using the mouse as a model system, we generated a prosthetic system that incorporates the code. This dramatically increased the system's capabilities-well beyond what can be achieved just by increasing resolution. Furthermore, the results show, using 9,800 optogenetically stimulated ganglion cell responses, that the combined effect of using the code and high-resolution stimulation is able to bring prosthetic capabilities into the realm of normal image representation.

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    • "Models like the DoG can be implemented using computationally cheap convolution methods and are often employed by the retinomorphic engineering community (e.g., Mead & Mahowald, 1988 ; Banks et al., 2005 ; Martínez et al., 2009 ). Models like the LN cascade (Nirenberg & Pandarinath, 2012 ) could be calculated effi ciently if tight constraints are placed on the processing boundaries. Otherwise the complexity scales linearly with the number of neurons simulated. "
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    ABSTRACT: The concept of visual restoration via retinal prosthesis arguably started in 1992 with the discovery that some of the retinal cells were still intact in those with the retinitis pigmentosa disease. Two decades later, the first commercially available devices have the capability to allow users to identify basic shapes. Such devices are still very far from returning vision beyond the legal blindness. Thus, there is considerable continued development of electrode materials, and structures and electronic control mechanisms to increase both resolution and contrast. In parallel, the field of optogenetics—the genetic photosensitization of neural tissue holds particular promise for new approaches. Given that the eye is transparent, photosensitizing remaining neural layers of the eye and illuminating from the outside could prove to be less invasive, cheaper, and more effective than present approaches. As we move toward human trials in the coming years, this review explores the core technological and biological challenges related to the gene therapy and the high radiance optical stimulation requirement.
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    • "These include artificial insemination and host mothering, cloning, gene manipulations, stem cell research and its use for therapy, and in the near future perhaps also selection of the gender of offspring, artificial womb, delay or prevention of aging, as well as assisted suicide and euthanasia, to mention just a few. It well may be that prostheses operated by will of amputees,39 devices that enable blind people to see,40 and technological intervention in depression,41 which all are blessed developments, may be the first attempts of intrusive intervention in the brain functions. This may lead to far-reaching and untoward territories and will pose a new array of ethical dilemmas to the society. "
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    • "However, it is well known that naturalistic visual experience relies not on the activity of any individual RGC but on diverse spatiotemporal patterns of activity in multiple distinct populations of RGCs. Thus, a central problem in producing high-resolution prostheses is to faithfully recreate spatiotemporal patterns of population activity in the output of the retina (Nirenberg and Pandarinath, 2012; Hottowy et al., 2012). Importantly , because different visual signals are conveyed to different targets in the brain by roughly 20 distinct types of retinal ganglion cells (see Dacey, 2004), a faithful reproduction of the retinal output must also respect the functional role of different cell types, particularly those that are likely to play an important role in human vision. "
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    ABSTRACT: Natural vision relies on spatiotemporal patterns of electrical activity in the retina. We investigated the feasibility of veridically reproducing such patterns with epiretinal prostheses. Multielectrode recordings and visual and electrical stimulation were performed on populations of identified ganglion cells in isolated peripheral primate retina. Electrical stimulation patterns were designed to reproduce recorded waves of activity elicited by a moving visual stimulus. Electrical responses in populations of ON parasol cells exhibited high spatial and temporal precision, matching or exceeding the precision of visual responses measured in the same cells. Computational readout of electrical and visual responses produced similar estimates of stimulus speed, confirming the fidelity of electrical stimulation for biologically relevant visual signals. These results suggest the possibility of producing rich spatiotemporal patterns of retinal activity with a prosthesis and that temporal multiplexing may aid in reproducing the neural code of the retina.
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