Immunocytochemical analysis of retinal neurons under electrical stimulation.

To function successfully, a retinal prosthesis needs to provide effective stimulation in a safe manner. To date, most studies have been dedicated to assessing proper stimulation parameters, for example, determining stimulus threshold. Few studies have looked at the effects of prolonged stimulation on retinal morphology. One previous study did show gross morphological changes in the rat retina due to mechanical pressure, with and without electrical stimulation (Colodetti, L., Weiland, J.D., Colodetti, S., Ray, A., Seiler, M.J., Hinton, D.R., Humayun, M.S., 2007). Here, we used immunocytochemistry to investigate the effects of the same experimental conditions on neuronal structure in finer detail. For this purpose, we first defined four experimental groups. In Group 1, the stimulating electrode was near but did not contact the retina, and we did not apply current pulses. In Group 2, the electrode also did not contact the retina, but we applied current pulses of 0.09 microC/phase. In Group 3, the stimulating electrode directly contacted the retina, but we did not apply current pulses. In Group 4, the stimulating electrode directly contacted the retina, and we applied current pulses of 0.09 microC/phase. We found neural damage only in the outer retina, including a disturbance of synaptic vesicle proteins in the photoreceptor terminals and a remodeling of horizontal and rod bipolar cells' processes. These results show that, although gross morphological changes are mainly concentrated around the area of electrode contact, immunocytochemistry can reveal changes in adjacent areas as well.