Abstract
Purpose :
To define the time-course of retinal degeneration using the electroretinogram (ERG), pupillary light reflex (PLR), and optical coherence tomography (OCT) in the rd10 mouse model of retinitis pigmentosa.
Methods :
Dark-adapted (DA) pupil responses were assessed using 300 ms red and blue flashes (luminance range: 0.001 to 1000 cd/m2). The maximum pupil constriction (MPC), a measure of combined photoreceptor and post-receptor function, was defined as the minimum pupil size following the flash. The post-illumination pupil response (PIPR), a measure of intrinsically photosensitive retinal ganglion cells (ipRGCs), was elicited by the highest luminance blue flash, and was defined as the difference between the MPC and the pupil size 6 to 8 sec after flash offset. ERGs were recorded and analyzed using conventional techniques. Rod-pathway function was assessed by measuring DA a- and b-waves for stimulus luminance of 0.001 to 30 cd.s.m2. Cone-pathway function was assessed by measuring light-adapted (LA) a- and b-waves for a 10 cd.s.m2 stimulus. OCTs were obtained and segmented to evaluate inner- and outer-retinal thickness. Pupil and OCT measurements were performed from 3 to 30 weeks of age, whereas ERGs were recorded from 3 to 10 weeks of age (N > 4 for all conditions).
Results :
The rd10 MPC and PIPR were reduced by 22% and 2% compared to the WT at week 3. The MPC continued to decline in the rd10 mice until approximately 6 weeks of age, after which it was extinguished. In contrast to the MPC, the PIPR was essentially normal at 3 weeks of age and did not decline over time. The rd10 DA ERG a- and b-waves were 77% and 65% smaller than the WT at 3 weeks of age (averaged across all luminance levels) and were extinguished by 5 weeks of age. The LA b-wave was reduced by 36% for the rd10 mice at 3 weeks of age and was extinguished by 5 weeks of age. Inner-retina thickness was generally normal at all ages for the rd10 mice, whereas outer-retina thickness was approximately 62% of the WT at week 3 and 30% of WT thereafter.
Conclusions :
The time-course of abnormality differed for the pupil, ERG, and OCT measurements. In rd10 mice, the loss of outer-retina function (ERG and MPC) is consistent with the observed outer-retina thinning, whereas the preserved PIPR is consistent with the generally normal inner-retina structure.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.