EAGER: Optofluidic Strategies for Therapeutic Delivery of Neurotransmitters to Restore Vision

视觉是我们日常生活中最重要、最复杂的感官。因此，不可逆的致盲疾病，如黄斑变性和视网膜色素变性，仅在美国就影响了1000多万人，对生活质量造成了毁灭性的后果。这些疾病中视力的丧失是由于视网膜中称为光感受器的细胞的进行性变性。光感受器通常将入射光信息转换为电化学信号，通过复杂的神经网络传递给大脑以感知视觉。即使神经网络的其余部分功能完好，变性也会导致神经网络的断裂，从而导致视觉过程的断裂。通过电流刺激存活细胞来替代退化细胞的视网膜植入物正在成为治疗这种失明的一种有希望的选择。但是，由于电流是一种非自然的刺激，他们很难恢复自然的视觉和低于法定失明限制的视觉敏锐度。PI小组最近的研究表明，用大脑化学物质谷氨酸刺激培养皿中的活视网膜组织，可以模拟视觉刺激后视网膜组织的自然激活。通过植入眼球后部的一个微小装置，用大脑化学物质人工刺激视网膜，有可能恢复比目前的视网膜假体更自然的视力和更好的视力。目前还缺乏一种合适的技术，可以通过眼睛内的植入式装置来输送化学物质。该项目旨在填补这一技术空白，探索仅使用穿过眼睛的自然光就能实现光控输送治疗量的大脑化学物质的策略。如果成功，该项目将加速可植入装置的开发，将大脑化学物质输送到视网膜，并帮助数百万因神经退行性视网膜疾病而失明的人恢复高灵敏度的自然视力。它还可能被证明对治疗其他神经退行性眼病有效，如青光眼和视神经炎，这些疾病阻止了视网膜假肢的使用，以及帕金森病和阿尔茨海默病等脑部疾病。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Vision is our most important and complex sense critical to daily living. Therefore, irreversible blinding diseases of the eye such as macular degeneration and retinitis pigmentosa that affect over 10 million people in the US alone have devastating consequences on the quality of life. Loss of vision in these diseases is due to progressive degeneration of cells called photoreceptors in the retina. The photoreceptors normally convert the incident light information into electrochemical signals that are relayed to the brain for the perception of sight through a complex neural network. Degeneration causes a break in the neural network and thereby the process of vision, even though the rest of the neural network is functionally intact. Retinal implants seeking to replace degenerated cells by stimulating surviving cells with electrical current are emerging as a promising option for treating such blindness. But, because current is an unnatural stimulus, they have difficulty restoring naturalistic vision and visual acuity below the legal blindness limit. Recent research from the PI's group has demonstrated that stimulating a live retinal tissue in a dish with the brain chemical glutamate mimics its natural activation following visual stimulation.Artificially stimulating the retina with brain chemicals delivered through a tiny device implanted in the back of the eye could potentially restore more naturalistic vision and better visual acuity than current retinal prostheses. A suitable technology for the delivery of chemicals through an implantable device in the eye, is currently lacking. The proposed project aims to fill this technological gap by exploring strategies that could enable light-controlled delivery of therapeutic amounts of brain chemicals using only natural light passing through the eye. If successful, this project could accelerate the development of an implantable device to deliver brain chemicals to the retina and help restore high-acuity naturalistic vision to millions of people who are blind by neurodegenerative retinal diseases. It could also potentially prove effective in treating other neurodegenerative eye diseases such as glaucoma and optic neuritis that preclude the use of retinal prosthetics and brain disorders such as Parkinson's and Alzheimer's diseases.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.