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Erica Landis, Hannah Lee Park, Li He, Curran Sidhu, Micah A Chrenek, Ryan Strickland, P. Michael Iuvone, Machelle T Pardue; Lens defocus alters dopamine synthesis under different ambient lighting conditions. Invest. Ophthalmol. Vis. Sci. 2018;59(9):750.
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© ARVO (1962-2015); The Authors (2016-present)
Different ambient light environments influence susceptibility to myopia. 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). This study aims to determine how illuminance and lens defocus alter dopamine (DA) synthesis, storage, uptake, and degradation and effect myopia susceptibility in mice.
Male C57BL/6J mice were housed in varied illuminance (photopic n=21, mesopic n=22, scotopic n=22) on a 12:12 L:D cycle beginning at post-natal day 23 (P23). A subset of mice received -10D lens defocusing goggles at P28 and refractive error was measured at P35. At P37 retinas were collected and examined by HPLC to determine changes in DA and DOPAC (a DA metabolite). Western blots were used to detect changes in protein levels related to dopamine synthesis (tyrosine hydroxylase, TH), and storage (vesicular monoamine transporter 2, VMAT2). Results were analyzed using two-way ANOVAs with Holm-Sidak post-hoc comparisons, reported here as mean ± SEM.
Photopic or scotopic illuminance decreased lens defocus myopia in mice (OD-OS, photopic: -2.60±0.54D, scotopic: -1.81±0.61D), compared to mesopic illuminance (-4.74±0.61D, p<0.005). Mice without lens defocus had similar refractive errors regardless of illuminance level. DA levels were stable across groups. DOPAC increased with illuminance regardless of lens defocus (p<0.001). TH in the active, phosphorylated state increased with lens defocus across all light levels (main effect of lens defocus, p=0.059). Mice with lens defocus exhibited a trend for lower levels of total TH protein after exposure to photopic or scotopic lighting compared to naïve mice, while levels remained unchanged in mesopic light. VMAT2 levels showed an opposite trend with higher levels with lens defocus compared to control in mesopic lighting and no change in photopic and scotopic.
These results suggest that lens defocus may alter dopamine synthesis. Proteins related to dopamine synthesis appear to be upregulated, and proteins related to storage downregulated, under lens defocus conditions, which may be dependent on ambient lighting conditions. Further research is needed to elucidate the complex signaling mechanisms that lead to reduced myopia susceptibility under photopic and scotopic conditions and the potential role of photoreceptor pathways.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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