Dopamine: Mechanistic Conundrums in Eye Growth Control

Abstract

Purpose : Diurnal patterns of retinal dopamine synthesis and release impact both diurnal retinal rhythms and refractive development. Because evolving evidence implicates both light exposures and circadian biology in refractive development, we assayed over a 24-hour cycle the vitreous levels of DOPAC (3,4-dihydroxyphenylacetic acid), a sensitive marker of retinal dopamine release.

Methods : Vitreous DOPAC was assayed in 12-day-old chicks reared under a 12-hour light:dark cycle. We tested 3 experimental monocular visual conditions known to alter refraction: diffusers, negative- or positive-lens wear; a fourth group was untreated “normal” controls. We sampled on the second day of device wear to isolate early signals modulating eye growth. After one full day of device wear, chicks were decapitated at 4-hour intervals over 24 hours (8 birds per time/condition). The vitreous was immediately isolated from each eye, flash-frozen and maintained frozen until assayed individually for DOPAC with HPLC-ED. Output was assessed by ANOVA and Generalized Estimating Equations.

Results : There was a diurnal rhythm in vitreous DOPAC levels in all groups (p<0.001 for each). In chicks with intact vision in both eyes, DOPAC levels were highest during the daytime in the light, lowest at night in the dark, and equivalent comparing the two eyes. Whether a unilateral growth stimulatory input (diffuser, negative lens) or growth inhibitory input (positive lens) was worn, vitreous DOPAC levels were reduced compared to contralateral eyes (p<0.001 for each cohort). With zeitgeber time (ZT)=0 at lights on, the time of peak DOPAC levels varied between experimental conditions: diffuser, broad peak ZT=4-12; negative lens, ZT=12; positive lens, ZT=8.

Conclusions : Retinal dopamine release oscillates in both eyes under normal conditions and under visual conditions that increase or decrease eye growth. Vitreous DOPAC levels are depressed in eyes during the early stages of altered visual input regardless of the direction of the visual effects on eye growth. These findings contradict the current hypothesis that retinal dopamine acts principally as a directional blur detector in emmetropization. Considering dopamine’s role in modulating diurnal retinal rhythms, these findings support a need to address circadian biology directly in ametropia mechanisms.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.