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

Bhuckory, M. B.; Wang, B.; Chen, Z. C.; Shin, A.; Pham-Howard, D.; Shah, S.; Monkongpitukkul, N.; Galambos, L.; Kamins, T.; Mathieson, K.; Palanker, D.

doi:10.1101/2023.07.25.550561

bioRxiv · 10.1101/2023.07.25.550561

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

Bhuckory, M. B.·Wang, B.·Chen, Z. C.·Shin, A.·Pham-Howard, D.·Shah, S.·Monkongpitukkul, N.·Galambos, L.·Kamins, T.·Mathieson, K.·Palanker, D.

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Abstract

Photovoltaic subretinal prosthesis (PRIMA) enables restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution limited by the 100 m pixel size. Since decreasing the pixel size below 75 m 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 m 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 m-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 m-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.

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Bhuckory, M. B., Wang, B., Chen, Z. C., Shin, A., Pham-Howard, D., Shah, S., Monkongpitukkul, N., Galambos, L., Kamins, T., Mathieson, K., Palanker, D.. 2023-07-28. 3D electronic implants in subretinal space: long-term follow-up in rodents. https://doi.org/10.1101/2023.07.25.550561

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