Modulation of All-Trans Retinoic Acid by Light and Dopamine in the Murine Eye.

Abstract

PURPOSE: Ambient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All-trans retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retinoscleral signaling cascade underlying myopic eye growth. However, how ocular atRA responds to different lighting and whether atRA and DA interact remains unknown. METHODS: Dark-adapted C57BL/6J mice (29-31 days old) were exposed to dim (1 lux), mid (59 lux), or bright (12,000 lux) ambient lighting for 5 to 60 minutes. Some mice were also systemically administered the DA precursor, LDOPA, or atRA before light exposure. After exposure, the retina and the back of the eye (BOE) were collected and analyzed for levels of atRA, DA, and the DA metabolite, DOPAC. RESULTS: DA turnover (DOPAC/DA ratio) in the retina increased in magnitude after only 5 minutes of exposure to higher ambient luminance, but was minimal in the BOE. In contrast, atRA levels in the retina and BOE significantly decreased with higher ambient luminance and longer duration exposure. Intriguingly, LDOPA-treated mice had a transient reduction in retinal atRA compared with saline-treated mice, whereas atRA treatment had no effect on ocular DA. CONCLUSIONS: Ocular atRA was affected by the duration of exposure to different ambient lighting, and retinal atRA levels decreased with increased DA. Overall, these data suggest specific interactions between ambient lighting, atRA, and DA that could have implications for the retinoscleral signaling cascade underlying myopic eye growth.