3D electronic implants in subretinal space : long-term follow-up in rodents

Bhuckory, Mohajeet and Wang, Bing-Yi and Chen, Zhijie Charles and Shin, Andrew and Pham-Howard, Davis and Shah, Sarthak and Monkongpitukkul, Nicharee and Galambos, Ludwig and Kamins, Theodore and Mathieson, Keith and Palanker, Daniel (2023) 3D electronic implants in subretinal space : long-term follow-up in rodents. Other. bioRxiv, Cold Spring Harbor, NY. (https://doi.org/10.1101/2023.07.25.550561)

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Photovoltaic subretinal prosthesis (PRIMA) enables restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution limited by the 100 μm pixel size. Since decreasing the pixel size below 75 μm in the current bipolar geometry is impossible, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime – up to 9 months post-implantation in aged rats. With both flat and 3D implants, VEP amplitude decreased after the day of implantation by more than 3-fold, and gradually recovered over about 3 months. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the second-order neurons. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices – 0.05 mW/mm2 with 10ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 5 months, before stabilizing at about 0.08 mW/mm2. Such threshold is significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.Competing Interest StatementDaniel Palanker and Ted Kamins- consultant (Pixium Vision) Daniel Palanker - Patent (Stanford University and Pixium Vision)