title: Pathology of damaging electrical stimulation in the retina.
abstract: The goal of this study was to examine the characteristics of electrically induced retinal damage. A retinal prosthesis must be both effective and safe, but most research related to electrical stimulation of the retina has involved measures of efficacy (for example, stimulus threshold), while relatively little research has investigated the safety of electrical stimulation. In this study, a single platinum microelectrode was inserted into the vitreous cavity of normally-sighted adult Long Evans pigmented rats. In one group of animals, no contact was made between the electrode and the retina and current pulses of 0.05 (n=3) and 0.2 (n=6) microC/phase were applied. In a second group, visible contact (slight dimpling of the retina) was made between the electrode and the retina and current pulses of 0.09 (n=4) microC/phase were applied. In both cases, stimulus pulses (biphasic, cathodic first, 1 ms/phase) were applied for 1 h at 100 Hz. Also, control experiments were run with no electrical stimulation with retina contact (n=4) and with no retinal contact (n=3). After stimulation, the animal was survived for 2 weeks with ocular photography and electroretinography (ERG) to document changes. During the follow-up period, retinal changes were observed only when the electrode contacted the retina, with or without electrical stimulation. No difference was noted in ERG amplitude or latency comparing the test eye to the stimulated eye. Histological analysis was performed after sacrifice at 2 weeks. A semi-quantitative method for grading 18 features of retina/RPE/choroidal appearance was established and integer grades applied to both test and control eyes. Using this method and comparing the most severely affected area (highest grade), significant differences (p<0.05) were noted between experiments with retinal contact and without retinal contact in all features except inner nuclear layer thickness. No difference was noted within a group based on the intensity of electrical stimulus applied. The size of the affected area was significantly larger with both retinal contact and electrical stimulation compared to with retinal contact alone. We conclude that mechanical pressure alone and mechanical pressure with excessive electrical stimulation causes damage to the retina but that electrical stimulation coupled with mechanical pressure increases the area of the damage.
authors.affiliation: Department of Ophthalmology, University of Southern California, 1355 San Pablo Street, Room 160, Los Angeles, CA 90033, USA.
authors.forename: L
authors.initials: L
authors.lastname: Colodetti
authors.forename: J D
authors.initials: JD
authors.lastname: Weiland
authors.forename: S
authors.initials: S
authors.lastname: Colodetti
authors.forename: A
authors.initials: A
authors.lastname: Ray
authors.forename: M J
authors.initials: MJ
authors.lastname: Seiler
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
authors.forename: M S
authors.initials: MS
authors.lastname: Humayun
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects*; D004566:Electrodes; D004596:Electroretinography / Q000379:methods; D005451:Fluorescein Angiography / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D010786:Photoreceptor Cells / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology