Subretinal Implantation Of Photovoltaic Arrays In Rats: In-vivo Imaging And Histological Analysis

Abstract

Purpose: : Close proximity between subretinal implant electrodes and bipolar cells is critical for efficient neural stimulation. Retinal inflammation, fibrosis or gliosis can have adverse effects on implant function. We evaluated the tissue response to subretinal implants having pixels separated by gaps of 5 and 10 μm.

Methods: : Silicon photodiode arrays or inactive SU-8 polymer coated with parylene were implanted through a sclerotomy into the subretinal space of wild type, P23H-1 and RCS rat eyes (n=31). Implants measured 0.8 x 1.2mm and 30μm in thickness, with pixel sizes of 60, 120 and 240μm separated by 5 or 10μm wide trenches. Eyes were followed by fundoscopic examination, fluorescein angiography and/or SD-OCT. Histology was performed on a subgroup with polymer implants after 8 weeks.

Results: : With both types of implants and in all three animal models retinas were edematous and showed some detachment over the implant immediately after surgery. OCT imaging revealed resolution of the retinal detachment within 3 weeks of surgery with the retina achieving close and uniform proximity to the upper surface of the array. Some eyes (n= 9) developed retinal thickening above the implant, likely caused by edema, fibrosis and/or vitreous traction. Fluorescein angiography revealed normal retinal vasculature above the device with some cases of vascular loss at the device edges. Histological analysis revealed very close apposition of the inner nuclear layer (INL) to the implant with retinal cells directly contacting the device. Some inner retinal cells migrated through the 10μm trenches into the subretinal space while fewer cells migrated through the 5μm trenches. Fibrotic and/or gliotic reactions formed around a portion of the implant in some retinas positioned close to the retinotomy site.

Conclusions: : Photodiode arrays were easily implanted in the subretinal space of rat eyes, with the inner nuclear layer located in close proximity to the electrodes. Greater migration of inner retinal cells into the subretinal space was observed through 10μm trenches compared to 5 μm trenches. Research is underway to evaluate the electrophysiological response to subretinal photovoltaic stimulation in-vivo, and prevent any fibriotic or gliotic reactions.

Keywords: retina • low vision • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)