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M.K. Kim, T.A. Walker, A.E. Faulkner, A.Y. Chow, V. Chow, G.Y. McLean, M.T. Pardue; Dose Response to Subretinal Electrical Stimulation in RCS Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1070.
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Neuropreservation of retinal function and structure in RCS rats following implantation of a microphotodiode array (MPA) has been suggested by previous studies (Pardue et al., 2005). Since microphotodiodes produce electrical currents in proportion to the intensity of incident light, increased light exposure may result in greater neuroprotective effects. Thus, in this study, we examined the dose response of subretinal electrical stimulation by exposing RCS rats implanted with MPAs to variable durations and combinations of two different lighting regimens: pulsing incandescent bulbs and flashes from the xenon bulb of an ERG Ganzfeld.
RCS rats were subretinally implanted at 21 days of age with active MPA devices (Optobionics Corp.) in one eye while the other eye served as an un–operated control. Rats were exposed to pulsing incandescent lighting (350 cd/m2 at 0.25 Hz) for 12 hrs/day (n=5), 1hr/day (n=8), or 1hr/wk (n=5). Retinal function was monitored using dark– and light–adapted ERG intensity series on a biweekly basis. Since the ERG flash (xenon bulb) also provided a source of MPA stimulation (9.5x10–4 to 137 cd sec/m2 at 0.1 to 2 Hz), an additional group of rats (n=6) received both ERG recordings and exposure to incandescent lighting each week. Rats were followed for 8 weeks.
There were no significant differences in ERG b–wave amplitudes among the implanted groups that received different incandescent light regimens. However, increased episodes of xenon flashes produced by ERG recordings resulted in significantly greater dark–adapted ERG b–wave amplitudes for the rats that received weekly versus biweekly ERGs.
While the incandescent lighting regimen provided stimulus current densities ∼300 times greater than those under normal environmental lighting, the regimen did not result in greater preservation of retinal function. However, the actual stimulus current dose delivered by the MPA device is unknown since light intensity varies considerably within the cage and the rats can freely avoid the light. In contrast, isolated xenon flashes, the brightest of which produce stimulus current densities ∼1500 times higher than those produced by the incandescent lighting, and which the rats could not avoid, resulted in increased preservation of retinal function. Future studies will confirm that neuroprotective effects are due to increased device output verus other unidentified aspects of the ERG procedure.
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