Abstract
Purpose :
The ability of cones to adapt to wide range of background lights and to dark-adapt rapidly make them perfectly suited for functioning as our daytime photoreceptors. The loss of cones severely affects the quality of life of patients with retinal degenerative diseases. Cone photoreceptors exploit autophagy to promote their continuous function in bright light, their resistance to light stress, and to maintain function during periods of metabolic crisis. Here, we examined the idea that autophagy might also support the rapid dark adaptation of cones that is critical for their function.
Methods :
We used in vivo ERG recordings to examine how the block of autophagy in Atg5-deficient cones or its upregulation by 24-hour fasting of mice with Atg5-proficient cones affects cone dark adaptation following exposure to bright bleaching light. Atg5 was deleted in cones by crossing Atg5-floxed mice (Atg5f/f) with the cone-specific HRGP-Cre mice. To facilitate cone recordings, all mice were on Gnat1 knockout background that blocks rod signaling.
Results :
Dark-adapted cones from Atg5-deficient (Atg5f/f HRGP-Cre+) mice had ERG b-wave amplitude and sensitivity comparable to these of Atg5-proficient (Atg5f/+HRGP-Cre+) controls. However, the recovery of sensitivity following exposure to bright bleaching light was significantly suppressed in Atg5-deficient cones. To upregulate autophagy, mice were fasted for 24 hours prior to the experiments. Surprisingly, fasting of mice with Atg5-proficient cones resulted in nearly 2-fold reduction in their dark-adapted sensitivity and 20% reduction in their maximal ERG b-wave response amplitude. In addition, cone dark adaptation was substantially accelerated in starved mice with Atg5-proficient cones compared to fed controls. In contrast, the dark-adapted responses from Atg5-deficient cones, or their recovery from a bright bleach were not affected by starvation.
Conclusions :
We find that the block of autophagy in cones results in suppressed cone dark adaptation. Conversely, upregulation of autophagy by starvation stress accelerates cone dark adaptation. In contrast, starvation of mice with Atg5-deficient cones has no effect on the kinetics of their dark adaptation. Our results reveal a surprising link between autophagy and dark adaptation in mouse cone photoreceptors and emphasize that autophagy is intimately involved in the daytime function of cone photoreceptors.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.