Talwar Sarah, Mazade Reece, Bentley-Ford Melissa, Yu Jianshi, Pilli Nageswara, Kane Maureen A, Ethier C Ross, Pardue Machelle T
bioRxiv. 2024 Dec 12:2024.12.06.627245. doi: 10.1101/2024.12.06.627245.
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- retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retino-scleral signaling cascade underlying myopic eye growth. However, how ocular atRA responds to different lighting and whether atRA and DA interact remains unknown.
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 5-60 minutes. Some mice were also systemically administered the DA precursor, LDOPA, or atRA prior to 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.
DA turnover (DOPAC/DA ratio) in the retina increased in magnitude after only five 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 to saline-treated mice, whereas atRA treatment had no effect on ocular DA.
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 retino-scleral signaling cascade underlying myopic eye growth.
环境光照暴露与儿童近视发展相关,并影响动物模型的近视易感性。目前,尚不清楚哪些信号介导了光照对近视的影响。全反式视黄酸(atRA)和多巴胺(DA)对实验性近视有相反的影响,可能参与了近视性眼球生长的视网膜-巩膜信号级联反应。然而,眼部atRA如何对不同光照做出反应以及atRA和DA是否相互作用仍不清楚。
将暗适应的C57BL/6J小鼠(29 - 31日龄)暴露于昏暗(1勒克斯)、中等(59勒克斯)或明亮(12000勒克斯)的环境光照下5 - 60分钟。一些小鼠在光照暴露前还全身给予DA前体左旋多巴(LDOPA)或atRA。暴露后,收集视网膜和眼后部(BOE)并分析atRA、DA和DA代谢产物3,4-二羟基苯乙酸(DOPAC)的水平。
暴露于较高环境亮度仅五分钟后,视网膜中的DA周转率(DOPAC/DA比值)大幅增加,但在BOE中最小。相比之下,随着环境亮度升高和暴露时间延长,视网膜和BOE中的atRA水平显著降低。有趣的是,与生理盐水处理的小鼠相比,LDOPA处理的小鼠视网膜atRA有短暂降低,而atRA处理对眼部DA没有影响。
眼部atRA受不同环境光照暴露持续时间的影响,且视网膜atRA水平随DA增加而降低。总体而言,这些数据表明环境光照、atRA和DA之间存在特定相互作用,这可能对近视性眼球生长的视网膜-巩膜信号级联反应有影响。