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A. Vankov, P. Huie, I. Hakim, D. Palanker; Retinal Damage Induced by Chronic Electrical Stimulation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1141.
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Purpose:Electronic retinal prostheses are under development for restoring some degree of vision in patients with retinal degeneration. Safety limits for electric stimulation of the retina are not well established. We study the threshold of retinal damage as a function of pulse duration and the size of the stimulating electrodes. Methods:To assess cellular damage produced by an electric field rather than toxicity of electrochemical products generated at the electrode–liquid interface, this study was conducted using glass pipette electrodes. Cellular damage zones were measured using Propidium Iodide fluorescent staining. Two types of tissue were used: chorioallantoic membrane of chicken embryo in–vivo (CAM – 30–70 µm thick membrane with epithelial and endothelial monolayers of cells on two sides), and retina of the chicken embryo in–vitro. Results:Minimal current density inducing cellular damage was detected with one pulse and with multiple pulses (7,500 pulses applied at 25 Hz during 5 min). Pulse duration ranged from 6 µs to 6 ms per phase and electrode diameters from 0.1 to 1 mm. Threshold current density was found to scale reciprocal to a square root of pulse duration for both the single pulse and multiple pulses. Threshold current density for single pulse varied between 0.21 A/cm2 at 6 ms to 5.8 A/cm2 at 6 µs. With multiple pulses the threshold varied between 0.065 A/cm2 at 6 ms to 1.3 A/cm2 at 6 µs. With large pipettes (0.35 – 1 mm in diameter) threshold current density was found to be practically independent of the pipette size, while with small pipettes (below 0.2 mm) it was rising reciprocal to the square of the pipette diameter, i.e. corresponding to the constant value of the total current. Conclusions:Retinal damage threshold was found to be significantly lower than current density applied for retinal stimulation in most of the published studies. In contrast to earlier reports , cellular damage by pulsed electric current is not determined by charge density, i.e. threshold current density is not reciprocal to pulse duration, but rather reciprocal to square root of pulse duration. Pipettes smaller than the distance to the target cells act as point sources and the damage threshold is determined by the total current rather than current density. 1. McCreery, D.B., Agnew, W.F., Yuen, T.G.H. & Bullara, L. Charge–Density and Charge Per Phase as Cofactors in Neural Injury Induced by Electrical Stimulation. IEEE Transactions On Biomedical Engineering 37, 996–1001 (1990).
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