Implants for Artificial Vision
Implants for Artificial Vision
Several research groups have demonstrated that electrical stimulation of the retina using implantable microelectrode arrays is a useful approach to specifically activate the visual cortex in animal experiments. It has been further shown that blind subjects suffering from retinitis pigmentosa do have phosphene perception when electrical current was applied to the retinal surface. Research groups and companies are currently testing implantable systems for electrical stimulation of the retina in blind patients suffering from retinitis pigmentosa in clinical trials. Recently published preliminary results revealed that the surgical procedures were well tolerated and that patients did have visual percepts, possibly helping to improve the patient's mobility and performance under daily-life conditions.
Although significant progress has been achieved in the treatment of eye diseases, there are still conditions threatening patients with the loss of sight. Among them, advanced cases of macular degeneration and diffuse progressive retinal dystrophies, such as retinitis pigmentosa (RP), are leading to blindness. Currently, wet forms of age-related macular degeneration are treated with repeated intravitreal injections of substances blocking the effect of VEGF, such as ranibizumab. However, in cases of photoreceptor death due to chronic edema, bleeding or decompensation of the retinal pigment epithelium (RPE), this treatment will fail. Furthermore, in dry age-related macular degeneration cases, where the RPE is lost, no treatment is available. The substitution of the RPE using transplants, such as autologous RPE sheets with or without choroid patches or in full macular translocation, cannot restore photoreceptor function once the photoreceptors are dead.
In genetically homogeneous diseases, such as Leber's congenital amaurosis, which is associated with the RPE65 mutation, gene therapy is currently being investigated by several groups after a functional improvement was seen in a dog model of that disease. From recent reports of these studies, it appeared that the adeno-associated virus-mediated application of the RPE65 gene is safe for patients and that there is some functional recovery. As these studies are still ongoing, it is too early to report a final result. Besides the safety discussion, another main issue is that the retinal dystrophies are genetically highly heterogeneous. In each case, the underlying mutation must be identified and a construct for gene therapy must be designed individually. Another problem is that the advanced cases may not benefit from gene therapy because the retina is already very much reorganized. The majority of photoreceptors are lost, and within the retina, functional changes occur, such as the migration of ganglion cells to more outer layers of the retina, the rewiring of retinal neurons, the manifestation of axon and/or dendrite conglomerates and new synapses. The retina in advanced cases of these dystrophies is not only without photoreceptors; it is heavily reorganized and remodeled. It is difficult to estimate the effect of putting several genes underneath such a reorganized retina. Owing to the limitation of these treatment strategies, the fact that techniques in retinal surgery were becoming simultaneously increasingly sophisticated and safe, and the fact that, at the same time, significant achievements were being made in micromachining and the fabrication of highly miniaturized electronic systems, some groups in the beginning of the 1990s came up with the idea of bypassing the lost retinal functions by coupling technical systems to neurons that were still functioning in the visual system. These ideas were also supported by early results of functional electrostimulation of the visual cortex in blind subjects.
Abstract and Introduction
Abstract
Several research groups have demonstrated that electrical stimulation of the retina using implantable microelectrode arrays is a useful approach to specifically activate the visual cortex in animal experiments. It has been further shown that blind subjects suffering from retinitis pigmentosa do have phosphene perception when electrical current was applied to the retinal surface. Research groups and companies are currently testing implantable systems for electrical stimulation of the retina in blind patients suffering from retinitis pigmentosa in clinical trials. Recently published preliminary results revealed that the surgical procedures were well tolerated and that patients did have visual percepts, possibly helping to improve the patient's mobility and performance under daily-life conditions.
Introduction
Although significant progress has been achieved in the treatment of eye diseases, there are still conditions threatening patients with the loss of sight. Among them, advanced cases of macular degeneration and diffuse progressive retinal dystrophies, such as retinitis pigmentosa (RP), are leading to blindness. Currently, wet forms of age-related macular degeneration are treated with repeated intravitreal injections of substances blocking the effect of VEGF, such as ranibizumab. However, in cases of photoreceptor death due to chronic edema, bleeding or decompensation of the retinal pigment epithelium (RPE), this treatment will fail. Furthermore, in dry age-related macular degeneration cases, where the RPE is lost, no treatment is available. The substitution of the RPE using transplants, such as autologous RPE sheets with or without choroid patches or in full macular translocation, cannot restore photoreceptor function once the photoreceptors are dead.
In genetically homogeneous diseases, such as Leber's congenital amaurosis, which is associated with the RPE65 mutation, gene therapy is currently being investigated by several groups after a functional improvement was seen in a dog model of that disease. From recent reports of these studies, it appeared that the adeno-associated virus-mediated application of the RPE65 gene is safe for patients and that there is some functional recovery. As these studies are still ongoing, it is too early to report a final result. Besides the safety discussion, another main issue is that the retinal dystrophies are genetically highly heterogeneous. In each case, the underlying mutation must be identified and a construct for gene therapy must be designed individually. Another problem is that the advanced cases may not benefit from gene therapy because the retina is already very much reorganized. The majority of photoreceptors are lost, and within the retina, functional changes occur, such as the migration of ganglion cells to more outer layers of the retina, the rewiring of retinal neurons, the manifestation of axon and/or dendrite conglomerates and new synapses. The retina in advanced cases of these dystrophies is not only without photoreceptors; it is heavily reorganized and remodeled. It is difficult to estimate the effect of putting several genes underneath such a reorganized retina. Owing to the limitation of these treatment strategies, the fact that techniques in retinal surgery were becoming simultaneously increasingly sophisticated and safe, and the fact that, at the same time, significant achievements were being made in micromachining and the fabrication of highly miniaturized electronic systems, some groups in the beginning of the 1990s came up with the idea of bypassing the lost retinal functions by coupling technical systems to neurons that were still functioning in the visual system. These ideas were also supported by early results of functional electrostimulation of the visual cortex in blind subjects.
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