Abstract
Purpose :
Retinitis pigmentosa (RP) is a degeneration characterized by progressive photoreceptor loss. In practice, a number of different electroretinography (ERG) protocols are used to assess the function of retinal neuronal cell types. It has previously been shown that the second harmonic (2F) of the photopic flicker is driven by inner retinal activity (e.g. retinal ganglion cells, amacrine cells), while the fundamental (F) harmonic is primarily driven by cone photoreceptors and bipolar cells. It is therefore possible to compare the loss of neural function differentially across both the outer and inner retina by comparing the F and 2F responses, respectively. Previous work indicated that there is a frequency dependence to the loss of F and 2F amplitudes in patients with RP. As the function of the inner retina may impact future strategies for treatment, we sought to characterize the frequency dependence of F and 2F in the rd10 mouse, a well-studied model of retinitis pigmentosa.
Methods :
All procedures involving animals were conducted under an approved NIH animal care protocol and following ARVO guidelines on the humane use of animals in ophthalmic and vision research. 3 week old rd10 mice and age-matched C57/Bl6 mice were used for this study. Mice were dark-adapted over-night and anesthetized by i.p. injection of ketamine (100 mg/kg)/xylazine (6 mg/kg) mixture. Pupils were dilated with 1% tropicamide and 0.5% phenylephrine. Animals were placed on a heating plate to keep body temperature at 37°C and all electrophysiological records were obtained with an integrated stimulator and light guide corneal electrodes (Celeris, Dianosys, LLC). Stimuli were flickered sinusoidally at different, closely spaced temporal frequencies between 2 and 31 Hz.
Results :
Rd10 mice exhibited robust photopic flicker responses at 3 weeks of age. Photopic flicker 2F amplitude losses in young rd10 mice exceeded F amplitude losses at 2, 3, and 11 Hz stimulus frequencies. For other stimulus frequencies, F and 2F amplitude losses were similar.
Conclusions :
F and 2F amplitude losses observed under photopic conditions in young rd10 mice were differentially affected by stimulus frequency, with low frequency stimuli revealing greater 2F amplitude losses. Monitoring inner and outer retinal function in the rd10 mouse requires careful consideration of temporal stimulus frequency.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.