Dopamine signaling and myopia development: What are the key challenges

Abstract

In the face of an “epidemic” increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this “myopia booming” and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children.

Growth in foetal life, infancy, and early childhood and the association with ocular biometry

“…Our observation that the highest association with CR was with weight at 1 year of age is in line with this finding. Emmetropisation is hypothesised to be an active process of ocular scaling resulting from environmental influences, release of retinal neurotransmitters and feedback mechanisms . The results of this study feed into this hypothesis, because we found a high correlation between body growth, corneal curvature, and AL without influence on AL/CR ratio.…”

“…Emmetropisation is hypothesised to be an active process of ocular scaling resulting from environmental influences, [25][26][27][28] release of retinal neurotransmitters [29][30][31] and feedback mechanisms. 32,33 The results of this study feed into this hypothesis, because we found a high correlation between body growth, corneal curvature, and AL without influence on AL/CR ratio. The small effect between birth weight and AL/CR ratio may be explained by lens parameters, as the lens is thinner with an increased birth weight.…”

Dopamine D1 Receptors Contribute Critically to the Apomorphine-Induced Inhibition of Form-Deprivation Myopia in Mice

“…APO, as well as dopamine, also produces more consistent and effective inhibition of myopia development than other dopamine agents for all species studied so far. 4 These results also support the idea that decreased dopamine activity contributes to the development of FDM.…”

“…3,4 Retinal and vitreous dopamine and/or the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) levels are reduced during the development of FDM in various animals, including chickens, 5,6 monkeys, 7 and guinea pigs. 8 Furthermore, the decrease of retinal DOPAC was restricted only to the deprived area of the retina during partial deprivation.…”

Myopia management in the Netherlands

“…There, re‐modulation of collagen structures takes place that makes the eye longer . The molecular structure of the signalling cascade is slowly becoming clearer, and dopamine is deemed to be an important player . Animal experiments have shown that this neurotransmitter is secreted by the amacrine cells after light exposure, and acts as a stop signal for growth .…”