Abstract
Purpose::
Electrical stimulation therapy (EST) has been associated with increased cell survival in sensory systems (vision, auditory) challenged by injury or toxic drugs. Rahmani et al. [ARVO 2005, 2006] reported that super-threshold, square-wave EST elicited both immediate (reduced ERG amplitude, glutamate depression) and long-term (preserved photoreceptor sensitivity, increased rate of cell loss) physiological responses. Based on these mixed results and reports of effects of exogenous electric fields applied to other cell types, the EST parameters were revised to be sub-threshold, low-frequency sine-wave currents. Immediate and long-term effects of this EST protocol are being evaluated using electroretinography and histology.
Methods::
Full-field corneal electroretinograms (ERG) measured in dark-adapted WT rats, before and immediately after 30 min of EST, were compared to results from animals receiving 30 min of background illumination instead of EST. Controlled-current sine-wave EST was delivered via a monopolar corneal electrode; currents ranged from ~1-17 µA (p-p, 5 Hz). P23H rats undergoing long-term EST therapy (30 min sessions 2x per week, begun at 4 wks of age), and control animals on the same anesthesia regimen, will be sacrificed at 16 wks and processed for histology.
Results::
One 30 minute session of EST did not result in reduced ERG b-wave amplitudes recorded immediately after EST delivery (p=0.581 (t-test), n=9), however b-wave latencies were decreased by 15-20%. Long-term effects of EST on rate of cell loss, and associated functional loss, will be compared to age-matched P23H controls and to results previously obtained with super-threshold square-wave EST.
Conclusions::
Low-current sine-wave EST has minimal immediate effects on the response of the retina to light stimuli, are considered sub-threshold, and are therefore consistent with exogenous electric fields investigated in other therapeutic contexts. Evaluation of long-term effects of this sub-threshold EST paradigm is in progress.
Keywords: neuroprotection • electroretinography: non-clinical • retinal degenerations: hereditary