Leong Audrey, Li Yueming, Ruikes Thijs R, Voillot Julien, Yuan Yuhao, Chen Guo, Facon Arnaud, Chhuon Chakrya-Anna, Joffrois Corentin, Tessier Gilles, Cornebois Marion, Dégardin Julie, Louise JeanDamien, Cheng Ji-Xin, Yang Chen, Moulet Hélène, Picaud Serge
Sorbonne Université, CNRS, INSERM, Institut de la Vision, F-75012 Paris, France.
Department of Electrical and Computer Engineering, Boston University, Boston, MA, 02215, United States.
bioRxiv. 2024 Nov 22:2024.09.03.611068. doi: 10.1101/2024.09.03.611068.
Retinal degenerative diseases of photoreceptors are a leading cause of blindness with no effective treatment. Retinal prostheses aim to restore sight by stimulating remaining retinal cells. Here, we present a photoacoustic retinal stimulation technology. We designed a polydimethylsiloxane and carbon-based flexible film that converts near-infrared laser pulses into a localized acoustic field with 56-μm lateral resolution, aiming at high-precision acoustic stimulation of mechanosensitive retinal cells. This photoacoustic stimulation resulted in robust and localized modulation of retinal ganglion cell activity in both wild-type and degenerated retinae. When a millimeter-sized photoacoustic film was implanted in the rat subretinal space, pulsed laser stimulation generated neural modulation along the visual pathway to the superior colliculus, as measured by functional ultrasound imaging. The biosafety of the film was confirmed by the absence of short-term adverse effects under optical coherence tomography retinal imaging, while local thermal increases were measured below 1 °C. These findings demonstrate the potential of photoacoustic stimulation for high-acuity visual restoration over a large field of view in blind patients.
光感受器的视网膜退行性疾病是导致失明的主要原因,且尚无有效治疗方法。视网膜假体旨在通过刺激剩余的视网膜细胞来恢复视力。在此,我们展示了一种光声视网膜刺激技术。我们设计了一种聚二甲基硅氧烷和碳基柔性薄膜,它能将近红外激光脉冲转换为横向分辨率为56微米的局部声场,旨在对机械敏感的视网膜细胞进行高精度声刺激。这种光声刺激在野生型和退化的视网膜中均导致视网膜神经节细胞活动的强烈且局部的调制。当将毫米大小的光声薄膜植入大鼠视网膜下间隙时,通过功能超声成像测量,脉冲激光刺激沿着视觉通路向上丘产生神经调制。在光学相干断层扫描视网膜成像下未发现短期不良反应,同时测得局部温度升高低于1℃,从而证实了该薄膜的生物安全性。这些发现证明了光声刺激在为盲患者进行大视野高敏锐度视觉恢复方面的潜力。