Abstract
Retinal prosthesis can restore partial vision in patients with retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Epiretinal prosthesis is one of three therapeutic approaches, which received regulatory approval several years ago. The thresholds of an epiretinal stimulation is partly determined by the size of the physical gap between the electrode and the retina after implantation. Precise positioning of epiretinal stimulating electrode array is still a challenging task. In this study, we demonstrate an approach to positioning epiretinal prostheses for an optimal response at the cortical output by monitoring both the impedance at the electrode-retina interface and the evoked-potential at the cortical level. We implanted a single-channel electrode on the epiretinal surface in adult rats, acutely, guided by both the impedance at the electrode-retina interface and by electrically evoked potentials (EEPs) in the visual cortex during retinal stimulation. We observe that impedance monotonously increases with decreasing electrode-retina distance, but that the strongest cortical responses were achieved at intermediate impedance levels. When the electrode penetrates the retina, the impedance keeps increasing. The effect of stimulation on the retina changes from epiretinal paradigm to intra-retinal paradigm and a decrease in cortical activation is observed. It is found that high impedance is not always favorable to elicit best cortical responses. Histopathological results showed that the electrode was placed at the intra-retinal space at high impedance value. These results show that monitoring impedance at the electrode-retina interface is necessary but not sufficient in obtaining strong evoked-potentials at the cortical level. Monitoring the cortical EEPs together with the impedance can improve the safety of implantation as well as efficacy of stimulation in the next generation of retinal implants.
Highlights
DEGENERATIVE retinal diseases can lead to significant loss of vision
The measured cortical evoked potentials (EEPs) is monotonically increased with electrode-retina impedance before its value reached 8 kΩ which is consistent with previous studies of epiretinal stimulation [23]
Our findings indicate two distinct trends: up to 8 kΩ EEP responses in visual cortex increase, but subsequently they decrease with increasing impedance
Summary
DEGENERATIVE retinal diseases can lead to significant loss of vision. Retinitis pigmentosa (RP) is an outer retinal disease in humans, characterized by the progressive deterioration and functional loss of rod and cone photoreceptors. Studies suggest that there is severe remodeling in the retina includes the ganglion cells [2, 3]. Recent evidence shows that some ganglion cells may retain their function [4, 5]. This suggested an opportunity to restore vision by bypassing damaged photoreceptors and directly activating the remaining inner retinal neurons. Though the correlation between electrode-retina distance and electrical thresholds of stimulation has been shown across numerous animal models including mammals [20,21,22] and rodents [2325], detailed studies of a range of electrode-retina proximity and its impact on cortical activation are limited
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