Levodopa Inhibits the Development of Form-Deprivation Myopia in Guinea Pigs

Mao, Junfeng; Liu, Shuangzhen; Qin, Wenjuan; Li, Fengyun; Wu, Xiaoying; Tan, Qian

doi:10.1097/opx.0b013e3181c12b3d

Cited by 78 publications

(27 citation statements)

References 54 publications

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“…In the present study, the decrease of myopic degree induced by citicoline is approximately 2.63D (from À3.25D to À0.62D) in the deprived eyes. This inhibitory effect looks more effective than that of levodopa (approximately 2.12D, from À3.62D to À1.5D), 19 a finding which requires further investigation. However, citicoline treatment cannot completely suppress the myopic development following form deprivation because there is a statistically significant difference between the deprived þ citicoline group and its normal control.…”

Section: Discussionmentioning

confidence: 86%

Citicoline retards myopia progression following form deprivation in guinea pigs

Mao¹,

Liu²,

Fu³

2016

Exp Biol Med (Maywood)

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The retinal dopaminergic system is involved in the myopic shift following form deprivation. Citicoline has been demonstrated to stimulate the dopaminergic system in the brain and retina. Furthermore, citicoline has been used in many neurogenic diseases, such as senile cognitive impairment, stroke and Parkinson's disease as well as in amblyopia and glaucoma. Our aim was to investigate the effect of citicoline on the refractive state and retinal dopamine level in form deprivation myopia of guinea pigs. Guinea pigs, at an age of four weeks, were randomly divided into normal control, deprivation, deprived + citicoline and deprived + vehicle groups. Form deprivation myopia was induced by a translucent eye shield covering the right eye. Citicoline was injected intraperitoneally twice a day (500 mg/kg, 9 am and 9 pm) for 10 days. In vitro, retinal explants were cultured with citicoline for 24 h, with a final citicoline concentration of 100 µmol/L. The ocular refractive parameters and retinal dopamine content were measured. After occlusion for 10 days, the form-deprived eyes became myopic with an increase in axial length and a decrease in retinal dopamine content. The intraperitoneal injection of citicoline reduced the myopic degree (from -3.25 ± 0.77D to -0.62 ± 0.47D, P < 0.001) and partially raised retinal dopamine levels (from 0.55 ± 0.21 ng to 0.81 ± 0.24 ng, P < 0.01) in the form-deprived eyes. After 24 h of culturing retinal explants with citicoline, retinal dopamine content increased significantly (from 0.42 ± 0.14 ng to 0.62 ± 0.21 ng, P < 0.05). These results demonstrated that an intraperitoneal injection of citicoline could retard the myopic shift induced by form deprivation in guinea pigs, which was mediated by an increase in the retinal dopamine levels.

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Section: Discussionmentioning

confidence: 86%

Citicoline retards myopia progression following form deprivation in guinea pigs

Mao¹,

Liu²,

Fu³

2016

Exp Biol Med (Maywood)

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“…In previous studies, other molecules had been used to study associations with axial elongation. In a study by Mao and colleagues, guinea pigs of an age of 4 weeks underwent form-deprived axial elongation and myopization (Mao et al, 2010). Repeated intraperitoneal injections of levodopa inhibited the axial elongation and significantly ( P < 0.001) reduced the myopic shift from − 3.62 ± 0.98 diopters to − 1.50 ± 0.38 diopters.…”

Section: Discussionmentioning

confidence: 99%

Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia

Jiang

Song

et al. 2017

EBioMedicine

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To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg) three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤ 1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.

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“…The first step in proving this hypothesis is to increase the overall availability of DA by injecting DA directly into the eye or using L-DOPA to increase DA synthesis. Such experiments have shown that increasing DA levels prevents FDM in guinea pigs (Mao et al, 2010), rabbits (Gao et al, 2006) and mice (Landis et al, 2016). Another approach is to increase DA signaling with a non-selective DA receptor agonists, such as apomorphine (APO) and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN).…”

Section: Effects Of Altered Da Levels On Myopic Eye Growthmentioning

confidence: 99%

“…This may be due to differences in drug concentrations and their affinities for the different DA receptors, or downregulation of DA receptors resulting from continuous occupation with minipump infusion. Additionally, APO and exogenous L-DOPA have no effect on refractive development when visual input is normal (Dong et al, 2011a; Mao et al, 2010; Rohrer et al, 1993; Yan et al, 2015a). Together these studies suggest that DA receptor activation is needed for normal refractive eye growth under challenging/abnormal visual conditions (FD or lens defocus) and that increasing DA levels in the eye can prevent myopic growth signals.…”

Section: Effects Of Altered Da Levels On Myopic Eye Growthmentioning

confidence: 99%

Dopamine signaling and myopia development: What are the key challenges

Zhou

Pardue

Iuvone

et al. 2017

Progress in Retinal and Eye Research

244

203

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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.

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Levodopa Inhibits the Development of Form-Deprivation Myopia in Guinea Pigs

Abstract: Systemic L-DOPA was partly effective in this guinea pig model and, therefore, is worth testing for effectiveness in progressing human myopes.

Cited by 78 publications

References 54 publications

Citicoline retards myopia progression following form deprivation in guinea pigs

Citicoline retards myopia progression following form deprivation in guinea pigs

Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia

Dopamine signaling and myopia development: What are the key challenges

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