Can light sensors, placed in ganglion cells, restore vision to a blind retina?

放置在神经节细胞中的光传感器能否恢复盲人视网膜的视力？

• 批准号: 7739334
• 负责人: William H Merigan
• 金额: $ 22.84万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739334
• 关键词: Address; Age related macular degeneration; Behavior; Behavioral; Biological Preservation; Blinded; Blindness; Cells; Characteristics; Complete Blindness; Development; Discrimination; Disease; Dropout; Electrodes; Exposure to; Eye; Eye diseases; Future; Human; Image; Injection of therapeutic agent; Lasers; Legal Blindness; Light; Macaca; Macular degeneration; Maps; Measures; Mediating; Methods; Mission; Modeling; Monkeys; National Eye Institute; Neurons; Ocular Prosthesis; Patients; Pattern; Photic Stimulation; Photoreceptors; Primates; Property; Prosthesis; Psychophysiology; Research; Research Project Grants; Research Support; Residual state; Resolution; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Retinitis Pigmentosa; Rodent; Structure of retinal pigment epithelium; Testing; Therapeutic; Tissues; Transfection; Viral Vector; Virus; Vision; Visual; Visual Cortex; Visual Perception; adaptive optics; base; behavior test; blind; density; ganglion cell; gene therapy; hereditary blindness; human subject; improved; innovation; light gated; nonhuman primate; optical imaging; photoreceptor degeneration; public health relevance; quantum; research study; restoration; retinal neuron; retinal rods; sensor

DESCRIPTION (provided by applicant): An exciting possibility, raised by the recent development of light-gated channels such as channelrhodopsin, is the restoration of visual sensitivity in patients that are blind due to degeneration of rod or cone photoreceptors or the retinal pigment epithelium (RPE) cells that nourish the photoreceptors. Development of such a therapeutic approach to blinding eye disease supports the mission of the National Eye Institute, which "supports research that helps .. treat eye diseases.. and ..leads to sight-saving treatment". Photoreceptor and RPE degeneration causes blindness in many common eye diseases, such as macular degeneration, as well as in blinding exposure to lasers or other intense lights. It is likely that the approach to restoring vision studied here is feasible, as shown by recent research in which light-gated channels were inserted into retinal cells of blind rodents and produced vision. The studies proposed here will test the quality of vision that can be produced by this approach in macaque monkeys, whose vision is virtually identical to human vision. The research plan involves creating small patches of blind retina in macaque monkeys, caused by photoreceptor/RPE damage due to prolonged exposure to a 568 nm laser. Initial studies will use visual testing to verify that the light-exposed regions of retina are completely blind. The light-gated channel channelrhodopsin2 will then be inserted into undamaged retinal ganglion cells overlying the regions of photoreceptor/RPE damage by intravitreal injection of AAV2 viral vector. Psychophysical testing will then measure the restored vision mediated by the channelrhodopsin and verify that there is no residual vision for wavelengths of light beyond that absorbed by channelrhodopsin. The actual restoration of vision by insertion of light-gated switches in humans will require a gene therapy approach, in which a virus containing the light switches was injected into the eye. This is the method being used in the present study, although with macaque monkeys rather than human subjects. If this approach is successful, applications to human vision could be initiated in the near future. PUBLIC HEALTH RELEVANCE: Degeneration of photoreceptor/RPE is the cause of blindness in common eye diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), prompting a search for a visual prostheses that can provide vision mediated by the surviving inner retinal neurons. The research proposed here will examine the possibility that visual perception can be restored by this prosthesis in macaque monkeys blinded by photoreceptor/RPE degeneration.

描述（由申请人提供）：最近开发的光门控通道（例如视紫红质）提出了一种令人兴奋的可能性，即恢复因杆状或锥状光感受器或视网膜色素上皮变性而失明的患者的视觉敏感性。 RPE）细胞滋养光感受器。这种致盲眼病治疗方法的开发支持了国家眼科研究所的使命，即“支持有助于..治疗眼病..并..导致挽救视力的治疗的研究”。光感受器和视网膜色素上皮变性会导致许多常见眼病失明，例如黄斑变性，以及暴露在激光或其他强光下导致失明。正如最近的研究表明，这里研究的恢复视力的方法是可行的，其中将光门通道插入盲人啮齿动物的视网膜细胞并产生视力。这里提出的研究将测试通过这种方法在猕猴身上产生的视觉质量，猕猴的视力几乎与人类的视力相同。该研究计划涉及在猕猴身上制造小块失明视网膜，这是由于长时间暴露在 568 nm 激光下导致光感受器/RPE 损伤造成的。初步研究将使用视觉测试来验证视网膜的曝光区域是否完全失明。然后，通过玻璃体内注射 AAV2 病毒载体，将光门控通道视紫红质 2 插入覆盖光感受器/RPE 损伤区域的未受损视网膜神经节细胞中。然后，心理物理测试将测量视紫红质通道介导的恢复视力，并验证超出视紫红质通道吸收的光波长没有残留视力。通过在人体中插入光门开关来实际恢复视力将需要一种基因治疗方法，其中将含有光门开关的病毒注射到眼睛中。这是本研究中使用的方法，尽管对象是猕猴而不是人类。如果这种方法成功，则可以在不久的将来启动对人类视觉的应用。 公共健康相关性：光感受器/RPE 退化是导致年龄相关性黄斑变性 (AMD) 和色素性视网膜炎 (RP) 等常见眼病失明的原因，促使人们寻找视觉假体，以提供由幸存的光感受器/RPE 介导的视力内部视网膜神经元。这里提出的研究将检验这种假体在因光感受器/RPE退化而失明的猕猴中恢复视觉感知的可能性。