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P. L. Axtell, J. Hetling, M. Baig-Silva; Subretinal Vision Prostheses: Contributions of Major Cell Types to the Electrically-Evoked ERG (eERG) Correlated With Progressive Cell Loss in P23h Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2546.
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In vivo electrophysiology was used to investigate the response of the retina to electrical stimulation. Understanding the electrically-evoked electroretinogram (eERG) will aid in evaluating efficacy of vision prostheses, especially in animal studies. Here, contributions of retinal cell types to the eERG were evaluated as a function of degeneration (i.e. cell loss) in the P23H rat.
Pigmented P23H (model of adRP) rats were acutely implanted with a subretinal electrode array positioned ~1-2 mm from the optic disc. Stimulus waveforms were biphasic pulses (100 µA; 100 µS per phase; bipolar 500 µm dia. electrodes) and the response of the retina recorded via a corneal electrode. Pharmacological dissection was employed (via intravitreal injection of PDA, Sodium Aspartate, NMDA and APB) to elucidate the cellular origins of the eERG response components. Changes in these components were compared with retinal cell loss (evaluated via histology) as a function of age.
The typical eERG response consists of three major components: N30, P75 and N105 (named according to polarity and latency), inhibited by PDA, APB, and NMDA, respectively. Amplitudes and latencies of these major components vary significantly as a function of age. Between ~6-32 weeks of age, the decrease in N30 and N105 amplitudes are reasonably well correlated with cell loss in the ONL and INL (0.74 ≤ R2 ≤ 0.82); both eERG components decreased more rapidly than cell number prior to ~16 weeks. The correlation between P75 amplitude and cell number is less strong (R2=0.67 for INL, 0.73 for ONL).
The eERG is distinct from the light-evoked ERG; pharmacological dissection suggests the following primary origins of eERG components: N30, HBC; P75, DBC; N110, 3rd order cells in ON pathway. Changes in eERG components with age are roughly correlated with the pattern of cell loss. High correlation with photoreceptor loss suggests that photoreceptor input strongly modulates the major eERG components, even though photoreceptor potentials do not contribute directly to the eERG waveform.
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