Morphological comparisons of flat and 3-dimensional subretinal photovoltaic arrays in rat and pig models of retinitis pigmentosa

Abstract

Purpose: Retinal prosthetics are designed to restore vision to patients with photoreceptor degeneration. Theoretically, close proximity of inner retinal cells to stimulating electrodes is needed for their optimal activation. We evaluated the morphology of retinas with subretinal inactive polymer arrays (IPAs) containing gaps between the pixels or pillar electrodes. In addition, we compared IPAs to active silicon photovoltaic arrays (PVAs) with only gaps.

Methods: IPAs or PVAs were implanted into the subretinal space of P23H-1 rats (8-11 wks of age) and P23H-1 transgenic and wildtype (WT) pigs (6-14 wks age). Implanted IPAs were either: (1) flat devices with 70 or 140 micron pixels separated by 5 or 10 micron gaps or (2) vertical pillar devices of various densities but without gaps. PVAs had a similar flat design. SD-OCT images visualized the placement of the implant 2 weeks after implantation and subsequently at regular biweekly intervals to monitor changes in retinal morphology. At the end of the experiment, rat (8 and 16 wks post-implantation) and pig eyes (2, 4 and 8 wks post-implantation) were enucleated and fixed. The tissue under the implant was examined in histological sections for migration of inner retinal cells through the implant gaps and any other morphological changes and compared to tissue near and distal to the implant.

Results: IPAs with 10 micron gaps showed significant migration of inner retinal cells to the RPE-side of the implant compared to 5 micron gap devices (36% vs 15%, p<0.001). Similar to IPAs, PVAs with 5 micron gaps showed little migration in rats or pigs. Surgical implantation of pillar devices was significantly more difficult than flat devices and created greater tissue trauma and glial reactions. In 38% of the cases, the ends of some pillars protruded through the rat retina over time.

Conclusions: The retinal response to PVAs or IPAs is similar. Ten micron gaps created significant inner retinal cell migration while 5 micron gaps allow close proximity of the inner retina to the device without excessive migration through the gaps. Flat devices with gaps are much easier to implant, they produced less trauma than the pillar arrays, and results in better inner retinal proximity.

Keywords: 688 retina • 696 retinal degenerations: hereditary • 540 glia