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

描述（由申请人提供）：最近光门控通道如通道视紫红质的发展提出了一个令人兴奋的可能性，即恢复由于杆状或锥状光感受器或滋养光感受器的视网膜色素上皮（RPE）细胞退化而失明的患者的视觉敏感性。开发这种治疗致盲眼病的方法支持了美国国家眼科研究所的使命，该研究所“支持有助于……治疗眼疾…和. .导致视力保护治疗”。光感受器和RPE变性导致许多常见眼病失明，如黄斑变性，以及暴露在激光或其他强光下致盲。最近的研究表明，将光门控通道插入失明啮齿类动物的视网膜细胞并产生视力，这可能表明这里研究的恢复视力的方法是可行的。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，猕猴的视觉几乎与人类的视觉相同。该研究计划包括在猕猴的视网膜上制造小块失明，这是由于长时间暴露在568纳米激光下造成的感光器/RPE损伤造成的。最初的研究将使用视觉测试来验证视网膜暴露在光线下的区域是否完全失明。然后通过玻璃体内注射AAV2病毒载体，将光门控通道通道rhodopsin2插入到覆盖于光感受器/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由通道视紫红质介导的恢复视力，并验证对于超过通道视紫红质吸收的波长的光没有残留视力。要想通过植入光控开关来真正恢复人类的视力，需要一种基因治疗方法，即将含有光控开关的病毒注入眼睛。这就是目前研究中使用的方法，尽管研究对象是猕猴而不是人类。如果这种方法是成功的，应用于人类视觉可以在不久的将来启动。

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.