3-dimensional subretinal prosthesis with single-cell resolution

Abstract

Purpose : In patients with geographic atrophy, planar subretinal photovoltaic implants with 100μm bipolar pixels provided prosthetic acuity up to 20/460, closely matching the pixel size. In rats, similar implants with 75 and 55μm bipolar pixels also demonstrated grating acuity matching the pixel pitch. However, stimulation threshold increases with decreasing size of bipolar pixel in planar implants, and it exceeds the electrode charge injection limit with pixels smaller than 40μm. To overcome this limitation, we developed 3-dimensional honeycomb-shaped electrodes. Retinal cells migrating of the into the honeycomb wells should experience a nearly uniform vertical electric field, resulting in a significantly lower stimulation threshold, independent of the pixel width. Here, we investigate the structural integration of the inner retinal cells with the wells matching the single cell size.

Methods : The 1 mm wide, 30 μm thick implants with 10 μm deep wells were fabricated in silicon, with wells diameter of 6, 8, 10 and 12 µm. Devices were implanted beneath the degenerate rat retina (RCS, p180-300) for 6 weeks, and then examined with confocal imaging of retinal whole mounts. The integration was quantified by counting the DAPI-positive nuclei within the wells. The cells populating the wells and the immune response were assessed on immunolabelled whole mounts with various cellular markers.

Results : The fraction of cell-filled wells increased with the pixel width: from 22% in 6 and 8 µm wells to 70% in 12 µm wells. The 10 µm wells had the best integration, with 60% of its cavities containing single cells, while in the 12 µm implants, more than half of the wells had more than one nucleus. The immune reaction to the implants was as mild as with planar arrays: 6% of the 10 µm wells were populated by IBA1 positive cells (microglia).

Conclusions : Honeycomb-shaped subretinal prostheses with 10 µm wide wells enable individual inner retinal neurons to migrate into the cavities that can contain active electrodes of individual pixels, which should allow single-cell stimulation. Since pixel size of 10 µm geometrically corresponds to visual acuity of about 20/40, this approach may enable highly functional restoration of central vision in patients with advanced age-related macular degeneration.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.