Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation

Abstract

Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP™, retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP™. The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P < 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P < 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P < 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.

Photoelectric Dye Used for Okayama University-Type Retinal Prosthesis Reduces the Apoptosis of Photoreceptor Cells

“…24 Our previous studies showed that the photoelectric dye-coupled films (OUReP) could reduce neuronal apoptosis. 15,16 In addition, the photoelectric dye could prevent retinal cells from death in mixed culture of glial cells and retinal neurons in vitro. 25 We, therefore, speculated that the photoelectric dye might become a new neuroprotective agent.…”

“…Behavioral tests might help evaluate the efficacy of the dye in RCS rats, as performed previously in RCS rats with the dye-coupled film implantation. 15,16 …”

“…12,13 Our previous studies showed that OUReP could reduce neuronal apoptosis in the eyes of Royal College of Surgeons (RCS) rats. 15,16 In this study, we tested whether intravitreous injection of the photoelectric dye would rescue photoreceptor cells from the apoptosis in RCS rats. 17–19 …”

Visual Evoked Potential Recovery by Subretinal Implantation of Photoelectric Dye‐Coupled Thin Film Retinal Prosthesis in Monkey Eyes With Macular Degeneration

“…In our previous studies, we showed vision recovery in retinal dystrophic rats (RCS rats) with dye‐coupled film implantation 26, 27, 28. In this study, the dye‐coupled films were implanted by vitreous surgery in the subretinal space of monkey eyes with cobalt chloride‐induced macular degeneration.…”

Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation

“…The prototype of the photoelectric dye-based retinal prosthesis, called Okayama University-type retinal prosthesis or OUReP™, is unique in using electric potentials to stimulate retinal neurons, in contrast with the other systems of retinal prostheses that generate electric currents [3–14]. The photoelectric dye is an organic molecule that absorbs light and converts light energy into electric potentials [3, 5, 10].…”