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: 7915440
• 负责人: William H Merigan
• 金额: $ 18.93万
• 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 2012-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915440
• 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(申请人提供)：最近发展的光门通道，如视紫红质，提出了一种令人兴奋的可能性，即由于视杆或视锥感光细胞或为感光细胞提供营养的视网膜色素上皮(RPE)细胞退化而失明的患者的视觉敏感度恢复。开发这样一种治疗失明眼病的方法支持了国家眼科研究所的使命，该研究所“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RPE变性会导致许多常见眼病的失明，如黄斑变性，以及暴露在激光或其他强光下的致盲。这里研究的恢复视力的方法很可能是可行的，正如最近的研究所表明的那样，在盲鼠的视网膜细胞中插入光门通道并产生视力。这里提出的研究将测试这种方法在猕猴身上产生的视觉质量，猕猴的视觉实际上与人类的视觉相同。这项研究计划包括在猕猴身上制造小块盲视视网膜，这是由于长时间暴露在568 nm激光下导致的光感受器/RPE损伤造成的。最初的研究将使用视觉测试来验证视网膜的光暴露区域是完全失明的。然后，通过玻璃体内注射AAV2病毒载体，将光门通道视紫红质2插入覆盖在光感受器/RPE损伤区域的未受损的视网膜神经节细胞中。心理物理测试将测量通道视紫红质调节的恢复视力，并验证除了通道视紫红质吸收的光以外的其他波长的光没有剩余视力。在人类体内通过插入光门开关来恢复视力需要一种基因治疗方法，即将含有光开关的病毒注射到眼睛中。这就是目前研究中使用的方法，尽管是针对猕猴而不是人类受试者。如果这种方法成功，在不久的将来就可以开始应用于人类视觉。 与公共卫生相关：光感受器/RPE的退化是导致老年性黄斑变性(AMD)和视网膜色素变性(RP)等常见眼病失明的原因，这促使人们寻找一种能够通过存活的视网膜内神经元调节视力的视觉假体。这里提出的研究将检验这种假体可以恢复因光感受器/RPE变性而失明的猕猴的视觉感觉的可能性。