Wearable Array for Ultrasound Stimulation on the Retina

涉及光感受器的进行性退化和功能丧失的视网膜变性是一种主要的 全球永久性视力丧失的原因。治疗这些不治之症的策略包括视网膜 通过在眼睛中植入装置电刺激存活的视网膜神经元的假体， 光遗传疗法和声遗传疗法。这些策略的现有挑战包括侵入性 复杂的植入手术和风险很大的基因治疗。因此，一种可以应用于 直接作用于天然存在的机械感受器以恢复盲人患者的视觉功能。 为此，几项先驱研究探索了超声刺激视网膜的可行性， 潜在地引起神经元活动[1 - 4]。然而，缺乏在体演示的视力恢复 以及以高时空分辨率从视网膜变性模型产生潜在图案 阻碍了US刺激作为有效视力恢复方法的作用。超越这些 局限性，在我们最近的研究[5]中，我们证明US是诱导神经元活动的有前途的方法 在体内的皇家外科学院（RCS）大鼠中，视网膜变性动物模型广泛用于 评估治疗效果。基于我们之前成功的演示，我们正在开发一种新的 用于视网膜上的超声刺激的可穿戴阵列。值得注意的是，我们的新设备是一个 以前作品的升级版。具体来说，在这个提案中，我们将工程师，设计， 制造我们设备的原型，用于技术验证、可靠性和功能评估。这 设备将包括用于捕获视觉场景的图像采集单元、用于 将视觉场景转换为超声刺激模式，以及赛车环透镜超声换能器阵列， 在视网膜上产生模式刺激。传感器是柔性的并且放置在眼球外部， 类似于接触透镜的应用。从换能器发射的超声波可以到达视网膜 而不穿过透镜，从而极大地减小了透镜中的声吸收。最后， 我们希望我们的发现能证明超声波刺激视网膜是一种安全有效的方法。 具有较高的时空分辨率，表明超声刺激作为一种新的 以及用于盲人患者平移应用的非侵入性视觉假体。

Retinal degeneration involving progressive deterioration and loss of function of photoreceptors is a major cause of permanent vision loss worldwide. Strategies to treat these incurable conditions incorporate retinal prostheses via electrically stimulating surviving retinal neurons with implanted devices in the eye, optogenetic therapy, and sonogenetic therapy. Existing challenges of these strategies include invasive manner, complex implantation surgeries, and risky gene therapy. Therefore, an approach that can apply directly to the naturally existing mechanoreceptors to recover visual function in blind patients is desired. For this purpose, several pioneer studies have explored the feasibility of US stimulation of the retina to potentially evoke neuron activities [1–4]. However, the lack of in vivo demonstration of vision restoration and potential pattern generation from retinal degenerative models at a high spatiotemporal resolution impeded the role of US stimulation as an efficient vision restoration approach. To move beyond these limitations, in our recent study [5], we demonstrated US as a promising approach to induce neuron activities in the Royal College of Surgeons (RCS) rat in vivo, a retinal degenerative animal model widely used for assessing therapeutic effects. Based on our previous successful demonstration, we are developing a novel wearable array for ultrasound stimulation on the retina. It should be noted that our new device is an upgraded version of previous works. Specifically, in this proposal, we are going to engineer, design, and fabricate a prototype of our device for technology validation, reliability, and functionality assessments. This device will consist of an image acquisition unit to capture the visual scenes, an image processing unit to convert visual scenes into ultrasonic stimulation patterns, and a racing ring lens ultrasound transducer array that generates patterned stimulation on the retina. The transducer is flexible and placed outside the eyeball, similar to the application of a contact lens. Ultrasound emitted from the transducer can reach the retina without passing through the lens, thus greatly minimizing the acoustic absorption in the lens. Ultimately, we hope our findings demonstrate that ultrasound stimulation of the retina is a safe and effective approach with a high spatiotemporal resolution, indicating a promising future of ultrasound stimulation as a novel and noninvasive visual prosthesis for translational applications in blind patients.