Abstract
Purpose :
Ambient light environments alter myopia susceptibility. We previously showed that photopic (15,000 lux) or scotopic (0.005 lux), but not mesopic (50 lux), ambient lighting protected mice from lens-induced myopia (ARVO 2015 E-Abstract #2152). Here we investigate the role of ambient light level on dopamine (DA) activity underlying the altered myopia susceptibility by examining DA activity after acute or long-term light exposure.
Methods :
Male C57BL/6J mice were placed in one of three illuminance conditions (photopic n=21, mesopic n=22, scotopic n=22) on a 12:12 L:D cycle beginning at post-natal day 23 (P23). Retinas were collected at three hours (acute) or twelve days (long-term). Levels of DA and DOPAC in the retinas were measured with HPLC. Digital droplet PCR and western blots were used to detect changes in gene expression and protein levels related to dopamine synthesis (tyrosine hydroxylase, TH), release (vesicular monoamine transporter 2), uptake (dopamine transporter), and degradation (monoamine oxidase). Results were analyzed using two-way ANOVA with Holm-Sidak post-hoc comparisons.
Results :
After acute light exposure, retinas in scotopic light showed significantly higher levels of DA (1.11 normalized to mesopic, p<0.01) and lower levels of DOPAC (0.48 normalized to mesopic, p<0.001) than mice housed in mesopic and photopic (DA: 0.86, DOPAC: 1.48 both normalized to mesopic). With long-term light exposure, differences in DA levels stabilized across groups. DOPAC was still lower in scotopic and higher in photopic conditions compared to mesopic light (p<0.001). An analysis of mRNA levels showed increasing expression of TH with increasing illuminance after long-term light but not acute exposure. Protein levels did not change with illuminance or duration of exposure.
Conclusions :
These results suggest that changes in dopamine dynamics with ambient lighting conditions are influenced by light exposure history. While retinal DA levels were stable across illuminance levels with long-term exposure, the different DA levels after acute exposure may indicate that the retina produces DA in anticipation of a particular light level based on light exposure history. While these results would suggest that higher DA activity under photopic lighting mediates the protective effects on lens-induced myopia, further research is needed to determine whether DA activity underlies the protective effects under scotopic lighting.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.