top of page
Search

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration

Won Gi Chung, Jiuk Jang, Gang Cui, Sanghoon Lee, Han Jeong, Haisu Kang, Hunkyu Seo, Sumin Kim, Enji Kim, Junwon Lee, Seung Geol Lee, Suk Ho Byeon, Jang-Ung Park | Nature Nanotechnology | 15 January 2024 | Vol 19 | Pages 688–697 | Link to article


Abstract

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm−2) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.


Main

Retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration, can cause gradual loss or permanent damage to photoreceptor cells, resulting in severe vision impairment1,2. However, the inner retinal neurons (ganglion and bipolar cells) can be preserved despite photoreceptor degeneration.


An electronic retinal prosthesis, which electrically stimulates inner retinal neurons using photoresponsive devices, has emerged as a promising method to restore vision3,4,5,6. The electrical activation of retinal neurons can generate visual perceptions (phosphene)7,8,9,10,11,12,13. This device has been adapted to human subjects blind by retinal degeneration, although still being limited by low visual acuity. The subretinal prosthesis, placed between the retinal pigment epithelium and the degenerated photoreceptor layer, provides stable mechanical fixation of the device, but has a greater degree of surgical difficulty with a limited implant size. The risks associated with subretinal implantation also include residual photoreceptor loss and retinal pigment epithelium disruption. Although subretinal implantation is routinely done in vitreoretinal surgery, the epiretinal prosthesis, placed inside the vitreous and facing the retinal ganglion cell (RGC) side, has shown promise in both long- and short-term clinical observations. However, the results have proven that one of the main limitations is caused by the unconformities between the retina and the implant, since the threshold to elicit retinal responses depends on the electrode–cell distance13,14,15,16,17,18. Low proximity resulting from these unconformities can also induce the lateral spread of the electric field, decreasing the spatial resolution of stimulation19,20. This imprecise stimulation on the epiretinal surface can excite the RGC axons, which traverse between the device and RGCs, generating irregular visual perceptions to patients21.


To enhance stimulation resolution and minimize axonal stimulation, it is important to establish a precise and stable contact and reduce the distance between the target RGC bodies and the stimulation electrodes, thereby reducing the activation thresholds of the RGC somas. However, patients with severe retinal degenerative diseases have locally non-uniform retinal surfaces, which can create an undesired geometrical gap between the retinal surface and stimulation electrodes19,22.



 

References

  1. He, S., Dong, W., Deng, Q., Weng, S. & Sun, W. Seeing more clearly: recent advances in understanding retinal circuitry. Science 302, 408–411 (2003).

  2. Bloch, E., Luo, Y. & da Cruz, L. Advances in retinal prosthesis systems. Ther. Adv. Ophthalmol. 11, 2515841418817501 (2019).

  3. Lee, G. J., Choi, C., Kim, D.-H. & Song, Y. M. Bioinspired artificial eyes: optic components, digital cameras, and visual prostheses. Adv. Funct. Mater. 28, 1705202 (2018).

  4. Sahel, J.-A. et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nat. Med. 27, 1223–1229 (2021).

  5. Rao, Z. et al. Curvy, shape-adaptive imagers based on printed optoelectronic pixels with a kirigami design. Nat. Electron. 4, 513–521 (2021).

  6. Ko, H. C. et al. A hemispherical electronic eye camera based on compressible silicon optoelectronics. Nature 454, 748–753 (2008).

  7. Lorach, H. et al. Photovoltaic restoration of sight with high visual acuity. Nat. Med. 21, 476–482 (2015).

  8. Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photon. 6, 391–397 (2012).

  9. Tang, J. et al. Nanowire arrays restore vision in blind mice. Nat. Commun. 9, 786 (2018).

  10. Jang, J. et al. Implantation of electronic visual prosthesis for blindness restoration. Opt. Mater. Express 9, 3878–3894 (2019).

  11. Maya-Vetencourt, J. F. Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy. Nat. Nanotechnol. 15, 30 (2020).

  12. Mandel, Y. et al. Cortical responses elicited by photovoltaic subretinal prostheses exhibit similarities to visually evoked potentials. Nat. Commun. 4, 1980 (2013).

  13. Sachs, H. G. & Gabel, V.-P. Retinal replacement—the development of microelectronic retinal prostheses—experience with subretinal implants and new aspects. Graefe’s Arch. Clin. Exp. Ophthalmol. 242, 717–723 (2004).

  14. Yue, L. et al. Ten-year follow-up of a blind patient chronically implanted with epiretinal prosthesis Argus I. Ophthalmology 122, 2545–2552.e1 (2015).

  15. Xie, H. et al. Monitoring cortical response and electrode-retina impedance under epiretinal stimulation in rats. IEEE Trans. Neural Syst. Rehabil. Eng. 29, 1178–1187 (2021).

  16. Lee, K.-W. et al. Pillar-shaped stimulus electrode array for high-efficiency stimulation of fully implantable epiretinal prosthesis. J. Micromech. Microeng. 22, 105015 (2012).

  17. Ahuja, A. K. et al. Factors affecting perceptual threshold in Argus II retinal prosthesis subjects. Trans. Vis. Sci. Technol. 2, 1 (2013).

  18. Ghani, N., Bansal, J., Naidu, A. & Chaudhary, K. M. Long term positional stability of the Argus II retinal prosthesis epiretinal implant. BMC Ophthalmol. 23, 70 (2023).

  19. Palanker, D., Vankov, A., Huie, P. & Baccus, S. Design of a high-resolution optoelectronic retinal prosthesis. J. Neural Eng. 2, S105–S120 (2005).

  20. Flores, T. et al. Optimization of pillar electrodes in subretinal prosthesis for enhanced proximity to target neurons. J. Neural Eng. 15, 036011 (2018).

  21. Esler, T. B. et al. Minimizing activation of overlying axons with epiretinal stimulation: the role of fiber orientation and electrode configuration. PLoS ONE 13, e0193598 (2018).

  22. Todorova, M. G., Scholl, H. P. N. & della Volpe Waizel, M. The impact of macular edema on microvascular and metabolic alterations in retinitis pigmentosa. Graefe’s Arch. Clin. Exp. Ophthalmol. 259, 643–652 (2021).


Comentarios

bottom of page