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失明治疗的人工视网膜系统_美国国家工程院2011年美国工程前沿研讨会上宣读的论文(节选)_英文原文_20120027-8

Retinal Prosthetic Systems for Treatment of Blindness
Jam es D. Weiland and Mark S. Huma yun
Doheny Eye Institute, University of Southern California
 
Most functions of the human body are controlled by small electrical signals delivered via nerves. Thus, it is no surprise that electrical signals applied to the body from external sources can modulate physiological activity. In fact, reports of such physiological electromodulation date back to the eighteenth century, but scientists of that time lacked the understanding of neurophysiology to understand the basic mechanism behind electricity’s ability to modulate biological activity. Advances in neurobiology, medicine, and engineering have allowed informed design of clinically beneficial implantable neurostimulation devices that are now used for a number of debilitating neurological diseases. Implantable neural stimulators activate nerve cells. Nerves are a class of cells responsible for processing and communicating information between the brain and other parts of the body (Kandel et al., 1991). Sensory receptors are specialized nerve cells that convert physical stimuli into electrical signals that can be relayed by other nerve cells to the brain. Nerve cells are polarized, meaning an electrical potential can be measured across the cell membrane. Transient changes in membrane potential signal to other cells that an event has occurred. Neural networks composed of connected neurons determine if that event, along with inputs from others cells, requires action by other parts of the nervous system. Diseases or injuries that damage nerve cells, particularly sensory cells, can result in significant disability for the affected individual, including loss of sensory input, diminished capability to process information, or reduced motor function. How can an electrical signal generated by an implanted device activate a nerve cell? It is not as simple as two wires being connected. Part of the complexity arises from the difference in electrical charge carriers; in metals, electrons carry charge, whereas in the body, ions carry charge. The conversion from electrons to ions occurs at the electrode, typically a metal or metal oxide, in direct contact with the extracellular fluid. An electrical signal applied to the electrode will cause current flow in the tissue via movement of charged ions, which include ions of sodium, chloride, and potassium, among others. The end effect of this charge movement is to depolarize the nerve cell membrane, after which the natural signaling mechanism of the nerve cell takes place and the brain, and person, observe an electrically elicited sensation or modulated function.
A number of successful neurostimulators are in widespread use. Cochlear implants stimulate the auditory nerve to give hearing to deaf people. Using these implants allows deaf people to hear so well that they can talk on a telephone.
Unrelenting pain sensations sometimes result from nerve damage or disease. Implantable devices that stimulate the lower spinal cord are known to decrease or even eliminate the feeling of pain. One of the most dramatic successes of electrical stimulation is in the treatment of Parkinson’s disease. By stimulating a part of the brain called the thalamus, many symptoms of Parkinson’s subside almost immediately. Parkinson’s patients with uncontrollable tremor or rigidity that severely limits motor function show improved coordination within minutes of commencing stimulation.
 
TREATING BLINDNESS WITH ELECTRICAL STIMULATION
The retina is the light-sensitive, multilayer tissue that lines the interior surface of the back of the eye (Figure 1) (see http://webvision.med.utah.edu/). Photoreceptors are the light-sensing cells of the retina, while the other cells process photoreceptor signals and send information to the brain via the optic nerve. When photoreceptors degenerate due to disease, the retina can no longer respond to light. However, the other nerve cells of the retina remain in sufficient numbers that electrical stimulation of these cells results in the perception of light. Blindness often results from progressive degeneration of the photoreceptors, which are the sensory nerves of the eye. Diseases like retinitis pigmentosa and age-related macular degeneration blind millions (Gehrs et al., 2010; Hartong et al., 2006). At first, symptoms are subtle, including difficulty seeing at night or blurred central vision. Ultimately, these conditions result in blindness. Given that vision is the sense by which people obtain most of the information about their environment, blindness has an extremely detrimental impact on the afflicted. Electrical stimulation has been proposed as a treatment for blindness for decades, but only recently have systems been implemented that are consistent with clinical deployment. This first documented use of electrical stimulation to create visual perception dates to 1755, when Charles LeRoy discharged a large capacitor through the head of a blind person, who described “flames descending downwards” (Marg, 1991). Over time, as science, medicine, and engineering progressed, feasibility of a permanent implant to stimulate the retina was established.
 
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