Abstract
Purpose :
It is well known in animals that photoreceptors shed their outer segment (OS) discs in a diurnal pattern, a process regulated by circadian control and light exposure. In humans, however, the influence of these factors is unknown. We used our recent discovery of the optical signature of disc shedding in the living human eye using adaptive optics-optical coherence tomography (AO-OCT) [1] to study this problem. We manipulated the onset of light exposure in three experiments to elucidate the role light plays in regulating the shedding process in entrained subjects.
Methods :
Six healthy subjects free of ocular disease were entrained to an 8/16 hour sleep/awake cycle (sleep: 11 pm-7 am), then imaged at 3° temporal retina (1.5°×1.5°) with the Indiana AO-OCT system. During each experiment, subjects were confined to indoor lighting (~700 lux). Experiment 1 established a baseline for shedding distribution across awake hours by imaging the same cone photoreceptors from 6 am to 11 pm every 15 minutes in four subjects. Experiment 2 delayed light onset by 6 hours in one eye by patching, and used the other (unpatched) eye as a control. We imaged both eyes of two subjects from 6 am to 6 pm every 30 minutes, removing the patch at noon. Experiment 3 advanced light onset by 3 hours and involved imaging one subject from 3 am to 12 noon every 15 minutes. In all three experiments we measured the number of shed cones and cone OS length at each time point.
Results :
We successfully imaged, tracked and quantified thousands of cones in each eye. Experiment 1: In all four subjects, shedding exhibited a diurnal rhythm, elevated in the morning and decreasing thereafter (6 am-12 noon: 46% shed; 12 noon-6 pm: 25% shed). Experiment 2: In the one subject analyzed, shedding in the unpatched eye was consistent with the diurnal rhythm observed in Experiment 1 (6 am-12 noon: 46% shed; 12 noon–6 pm: 31% shed). In sharp contrast, in the patched eye, shedding was delayed by about 6 hours (6 am-12 noon: 28% shed; 12 noon-6 pm: 51% shed). Experiment 3: Shedding was reduced at all time points and no diurnal rhythm was observed (3 am-12 noon: 28% shed).
Conclusions :
Shifting the time of light onset immediately alters the normal diurnal rhythm of cone shedding, either by shifting or disrupting it. Light plays a dominant role in regulating shedding in humans.
[1] Kocaoglu, et al. Biomed. Opt. Express 7.11 (2016): 4554-68.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.