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一种灵活的高精度光声视网膜假体。

A flexible high-precision photoacoustic retinal prosthesis.

作者信息

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

机构信息

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.

出版信息

bioRxiv. 2024 Nov 22:2024.09.03.611068. doi: 10.1101/2024.09.03.611068.

DOI:10.1101/2024.09.03.611068
PMID:39282448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398364/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/ab804b5ae082/nihpp-2024.09.03.611068v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/055631a0281b/nihpp-2024.09.03.611068v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/f77c36aa16af/nihpp-2024.09.03.611068v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/2bad2a9c5158/nihpp-2024.09.03.611068v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/5b881b7597bf/nihpp-2024.09.03.611068v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/489fd60f8b01/nihpp-2024.09.03.611068v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/ab804b5ae082/nihpp-2024.09.03.611068v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/055631a0281b/nihpp-2024.09.03.611068v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/f77c36aa16af/nihpp-2024.09.03.611068v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/2bad2a9c5158/nihpp-2024.09.03.611068v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/5b881b7597bf/nihpp-2024.09.03.611068v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/489fd60f8b01/nihpp-2024.09.03.611068v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7479/11589944/ab804b5ae082/nihpp-2024.09.03.611068v2-f0006.jpg

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本文引用的文献

1
High-Precision Photoacoustic Neural Modulation Uses a Non-Thermal Mechanism.高精度光声神经调节使用非热机制。
Adv Sci (Weinh). 2024 Aug;11(32):e2403205. doi: 10.1002/advs.202403205. Epub 2024 Jun 26.
2
Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up.4年随访时,PRIMA视网膜下微芯片用于萎缩性年龄相关性黄斑变性患者的假体视力
Ophthalmol Sci. 2024 Mar 7;4(5):100510. doi: 10.1016/j.xops.2024.100510. eCollection 2024 Sep-Oct.
3
Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.
非侵入式影像引导超声神经刺激,可实现任意 2D 图形,及其在高质量视力恢复中的应用。
Nat Commun. 2024 May 27;15(1):4481. doi: 10.1038/s41467-024-48683-6.
4
Photoacoustic: A Versatile Nongenetic Method for High-Precision Neuromodulation.光声:一种用于高精度神经调节的多功能非遗传方法。
Acc Chem Res. 2024 Jun 4;57(11):1595-1607. doi: 10.1021/acs.accounts.4c00119. Epub 2024 May 17.
5
Noninvasive Ultrasound Retinal Stimulation for Vision Restoration at High Spatiotemporal Resolution.用于高时空分辨率视觉恢复的非侵入性超声视网膜刺激
BME Front. 2022 Feb 21;2022:9829316. doi: 10.34133/2022/9829316. eCollection 2022.
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Cellular migration into a subretinal honeycomb-shaped prosthesis for high-resolution prosthetic vision.细胞向视网膜下蜂窝状假体中迁移,以实现高分辨率假体视力。
Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2307380120. doi: 10.1073/pnas.2307380120. Epub 2023 Oct 13.
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Polydimethylsiloxane as a more biocompatible alternative to glass in optogenetics.聚二甲基硅氧烷作为光遗传学中比玻璃更具生物相容性的替代品。
Sci Rep. 2023 Sep 26;13(1):16090. doi: 10.1038/s41598-023-43297-2.
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Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.视网膜假体:视觉恢复的工程与临床视角。
Sensors (Basel). 2023 Jun 21;23(13):5782. doi: 10.3390/s23135782.
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Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo.视觉皮层的非侵入性混合超声体内刺激
Bioengineering (Basel). 2023 May 10;10(5):577. doi: 10.3390/bioengineering10050577.
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J Neural Eng. 2023 Jun 1;20(3). doi: 10.1088/1741-2552/acd7a4.