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J.G. Eng, F.N. Ross–Cisneros, D. Güven, J.D. Weiland, M.S. Humayun, A.A. Sadun; Evaluation of Optic Nerve Integrity in Normal–Sighted Dogs After Acute Implantation and High Current Electrical Stimulation by an Epiretinal Array . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1535.
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To determine the electrical stimulation levels required to produce optic nerve degeneration in normal–sighted dogs after acute implantation of a weighted epiretinal array.
Four normal–sighted dogs were used. In three dogs, the right eye was implanted with an epiretinal array and stimulated for four hours with maximum electrical pulses of 2 mA, 1 ms/phase biphasic pulses. The electrode array was held against the retina with a gold weight attached to the back of the array. After four hours of implantation and stimulation, the array was removed and the dog was followed for 30 days before terminal surgery. Immediately prior to euthanasia, the same implantation procedure was applied to the left eye with the same stimulation for four hours. For the last dog, the right eye had four hours of stimulation with maximum electrical pulses of 2 mA with a 23–day follow–up and there was no implantation to the left eye. All eyes were enucleated at terminal surgery. Optic nerves were nicked peripherally to denote inferior and nasal aspects, fixed in half–strength Karnovsky’s, and then processed and embedded. Sections were cut at 1.5 µm and stained with p–phenylenediamine (PPD). Degenerated axon profiles in each quadrant of an optic nerve section were manually counted using a light microscope at 1,250X magnification.
Optic nerves from left eyes that were either stimulated immediately prior to euthanasia or were not implanted served as controls since the four hour window before sacrifice was negligible for optic nerve degeneration to occur. Epiretinal array implantation followed by electrical stimulation with maximum current of 2 mA was associated with a statistically significant increase in the number of degenerated axon profiles in the corresponding optic nerve (3,700 for acute stimulation vs. 652 for controls, p<0.05). The optic nerve quadrant(s) that corresponded to the site of array placement and stimulation consistently demonstrated the greatest increase in the number of degenerated axon profiles when compared to the same quadrant in the fellow control eye.
Epiretinal array implantation with a weighted array followed by acute electrical stimulation at high currents up to 2 mA led to axonal degeneration in the corresponding quadrant(s) of the optic nerve. Further studies are needed to establish dose effects of electrical stimulation and to further elucidate the role and extent of surgical implantation on axonal degeneration.
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