Abstract
Purpose :
The circadian clock plays important roles in the regulation of retinal functions. Previous studies have indicated that removal of the clock gene, Bmal1, from the retina alters photosensitivity, spectral identity and cone viability. We have previously reported that environmental circadian disruption (ECD) also affected circadian clocks in retina and retinal pigment epithelium (RPE). ECD also affected retinal function by altering peripheral retinal circuitry. In this study we investigated whether the re-exposure to stable light cycle is able to re-entrain circadian clocks in the eye and rescue retinal function after ECD.
Methods :
PER2::LUC and C57BL/6 mice were placed in a light tight isolated chamber and expose to ECD light cycles by advancing the time of light-on at 6 hours/week for 4 weeks. For control group, mice were exposed to a 12/12 Light/Dark (LD) cycle without any shifts. After the end of ECD cycle, mice were re-exposed to a 12/12 LD cycle for two to four weeks. Then after two or four weeks, PER2::LUC mice (3-4 mo. old) were sacrificed and the retina and the RPE were isolated and cultured for bioluminescence measurement. C57BL/6 mice (3-4 mo. old) were also subjected to both scotopic and photic electroretinogram (ERG).
Results :
The circadian rhythm in PER2::LUC bioluminescence revealed that re-exposure of stable light cycle for two weeks re-entrained circadian clock in the retina and RPE. Two weeks of re-exposure to a 12/12 LD cycle did not rescue the amplitude of scotopic b-wave after ECD, but after four weeks of re-exposure to a 12/12 LD the amplitude of scotopic b-waves did not show any difference with respect to control group.
Conclusions :
Our data indicates that two weeks of exposure to a 12/12 LD after ECD re-entrains circadian clocks in retina and RPE and the re-entrainment ocular clock rescues the retinal functioning. Thus, our results suggest that ECD induced visual impairment can be reversed by the stable light cycle.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.