Electrical Stimulation Alters Outer Retina Morphology

Abstract

Purpose: : To evaluate retina morphology after electrical stimulation with an epiretinal electrode.

Methods: : All experiments conformed to ARVO guidelines. A disk electrode (75 µm diameter Pt/Ir) was inserted into the vitreous cavity of adult Long Evans pigmented rats. Experiments were categorized into four groups: Group1-electrode placed near the retina without any physical contact or stimulation (n=4); Group2-electrode placed near the retina without any physical contact and delivered current pulses of 0.09µC/phase (n=4); Group3-electrode made a physical contact with the retina but no current pulses were delivered (n=4) and Group4-electrode made a physical contact with the retina and also delivered current pulses of 0.09µC/phase (n=4). The electrode was kept in position for 1-hour period with or without current stimulation (cathodic-first, charge-balanced current pulses at 100 Hz). After 2 weeks recovery period we performed immunohistochemistry to investigate in finer details, the effects of stimulation on the anatomy of retinal neurons.

Results: : Except in Group1, changes were observed in the retina morphology due to either stimulation or electrode contact or both in areas directly contacted by the electrode and also in adjacent sections. First, we observed that mechanical pressure and electrical stimulation each can cause gliosis. We also observed that although the stimulation electrode was placed near the ganglion-cell layer, the only observed neural cell damage was in the outer retina. This damage included loss of photoreceptor cells indicated by abnormal dispersion of immunoreactive puncta labeled for SV2A and SV2B in the ONL of group 3 and 4 retinae. Also sections immunolabeled for PKCα showed the dendritic arbors of the rod bipolar cells oriented towards the middle of the ONL while sections immunolabeled for calbindin showed sprouting of processes from horizontal cells oriented towards the ONL, indicating remodeling of rod bipolar cells and horizontal cells. This is in contrast to our previous finding where we found changes in the gross morphology of the retina only in areas directly contacted by the electrode (Colodetti et al., 2007).

Conclusions: : Both electrode contact alone and along with high intensity stimulation cause changes in the retina. Although the electrode is placed on the ganglion cell side, changes are observed in the outer retina.

Keywords: immunohistochemistry • bipolar cells • ganglion cells