LONG–TERM NEUROPROTECTIVE EFFECT OF THE SUBRETINAL IMPLANT IN THE RCS RAT

Abstract

Abstract: : Purpose: We previously demonstrated that implantation of the subretinal artificial silicon retina (ASR) microchip induces preservation of retinal function and photoreceptor cells in RCS rats up to 11 weeks of age (Pardue et al., 2003; ARVO). The goal of this study was to evaluate the long–term neuroprotective effects of the subretinal ASR chip in RCS rats up to 21 weeks of age. Methods: Three–week–old RCS rats were implanted with an active ASR chip (n=10) in one eye while the contralateral eye was implanted with an inactive ASR chip (n=5) or underwent sham surgery (n=5); three rats served as unoperated controls. Retinal function was monitored biweekly via ERGs until 18 weeks post–implantation, at which time the animals were euthanized. Eyes were enucleated, processed into plastic and sectioned in order to count photoreceptor nuclei. Results: As photoreceptor degeneration progressed, retinal function declined in all groups with time. In contrast with previous reports, ERG data showed no significant functional differences between groups at any time points. However, eyes implanted with active and inactive ASR chips were found to have significantly larger numbers of photoreceptors than unoperated control eyes. Additionally, sham–operated eyes were found to have significantly greater density of photoreceptors in the area of the incision compared to unoperated eyes. The preservation in the sham–operated eyes was also greater than that in active and inactive eyes, however, the region of preservation in sham–operated eyes was restricted to a localized area at the incision compared to a larger region surrounding the implant in the ASR–implanted eyes. No significant differences in photoreceptor numbers were found between eyes implanted with active and inactive ASR chips. Conclusions: These results suggest that neuroprotection from the ASR chip, at least in the RCS rat, may primarily be due to the mechanical presence of the device in the subretinal space rather than from electrical stimulation.

Keywords: neuroprotection • anatomy • retinal degenerations: cell biology