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Joseph Majdi, Wai T Wong, Daniel X Hammer, Ethan D Cohen; Microglial Response to Electrical Overstimulation by Epiretinal Stimulus Electrodes in the Adult Rabbit Retina.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1821.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal microglia are macrophage-like sentinel cells that produce dramatic morphological changes when they detect tissue injury. We examined the sensitivity of the retinal microglia to detecting retinal damage from electrical overstimulation by epiretinal prosthesis electrodes.
Using a superfused adult rabbit eyecup preparation and Ames media, we electrically overstimulated small retinal regions at ½ hour to hour intervals in order to study how microglia respond temporally to retinal damage from overstimulation by stimulus electrodes. Using optical coherence tomography, a 380μm i.d. transparent fluopolymer tube electrode was positioned close to the retina surface and a series of 749μC/cm2/ph biphasic current pulses at 50Hz were applied to the local retina for 5 minutes, resulting in the formation of a series of ring-like lesions. The retinal locations of the tube position/lesions were recorded. To label the microglia, the rabbit eyecup was incubated with dye-conjugated Griffonia Isolectin B4 either live or post-fixation. The microglia around damage zones were reconstructed in detail using confocal microscopy z-stacks and analyzed for changes in morphology and position. A total of 18 zones were analyzed.
In the normal rabbit retina, microglia were regularly distributed across the inner retinal surface. In response to electrical overstimulation, microglia from adjacent retinal locations migrated to the periphery of the damage zone and oriented their processes toward the center of the lesion. At 30 min post-stimulation, microglia processes were thin and showed little orientation. By 2 hours post stimulation, microglial processes had oriented their processes toward the periphery of the damage zone. By 4 hours, most microglia had thickened processes and had migrated close to the lesion edge. A few microglia entered the zone’s center.
Microglia are sensitive indicators of retinal injury by electrical overstimulation. In adult rabbit tissue, morphological changes in response to overstimulated retinal regions occur on the order of one hour or less. Future studies will examine the sensitivity of retinal microglia in real time in response to electrical stimulation.
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