Abstract
Purpose :
Previous studies have explored oscillatory action potential discharges in retinal ganglion cells (RGCs) of photoreceptor-degenerated (PD) retinas across various rodent models, which can degrade signal interpretation from the retina to higher visual pathways. However, the S334ter rat model, with a common rhodopsin mutation in human retinal degeneration, remains unexamined. This study focuses on the oscillatory behavior of S334ter RGCs, postulating a different pattern from other PD models.
Methods :
Our analysis focused on the neural activity of RGCs in S334ter rat retinas (N=37 hemizygous; N=15 homozygous), ranging from PND 14 to 170. Long-Evans rats (N=30) were the control group. The retinal tissues were extracted and positioned on an 8x8 multielectrode array, which was constantly perfused with oxygenated Ames medium. MC_Rack software (Multichannel Systems, GmbH) was used to record the spontaneous response of RGCs. The oscillatory firing pattern was quantified by interspike interval histogram, power spectral density, auto- and cross-correlograms.
Results :
S334ter RGCs have lower spontaneous activity than wildtype RGCs and fired in an oscillatory fashion. The oscillation frequency decreased from 9 to 4 Hz during early degeneration (PND 14-16), then stabilized at 5 Hz. Oscillatory amplitude grew from PND 14-45 but then declined, disappearing by PND 125. Cross-correlograms revealed anti-phased patterns between correlated (presumed ON/ON and OFF/OFF) and anti-correlated (presumed ON/OFF) RGC pairs. The oscillation propagated up to 1.5 mm across the retina.
Conclusions :
S334ter RGCs exhibit hypoactivity, unlike the hyperactivity seen in rd1 and rd10 mouse models. Oscillation frequency changes correlate with the rate of rod apoptosis. Oscillation cessation in late-stage degeneration might link to AII amacrine cell migration. These widespread oscillatory activities need consideration for the design of retinal prostheses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.