Studies on retinal mechanisms possibly related to myopia inhibition by atropine in the chicken

Mathis, Ute; Feldkaemper, Marita; Wang, Min; Schaeffel, Frank

doi:10.1007/s00417-019-04573-y

Cited by 32 publications

(49 citation statements)

References 72 publications

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“…Conversely, retina-specific tyrosine hydroxylase knockout mice and mice treated with 6-hydroxydopamine, which depletes the retina of dopaminergic neurons, show a myopic shift in refraction 15 , 29 . Furthermore, the ability of bright light to inhibit FDM through increased dopamine release 30 – 33 is inhibited by the administration of dopaminergic antagonists in chicks and mice 34 , 35 . Similarly, the protective effects of brief periods of normal vision against the development of FDM in chicks is lost by modulating dopaminergic function by either keeping the animals in the dark during diffuser removal, thus inhibiting dopamine release, or by injecting a dopaminergic D2-like receptor antagonist 19 .…”

Section: Introductionmentioning

confidence: 99%

Levodopa inhibits the development of lens-induced myopia in chicks

Thomson

Morgan

Karouta

et al. 2020

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Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of myopia (short-sightedness). We have previously demonstrated that topical application of levodopa in chicks can inhibit the development of form-deprivation myopia (fDM) in a dose-dependent manner. Here, we examine whether this same protection is observed in lens-induced myopia (LiM), and whether levodopa's protection against fDM and LiM occurs through a dopamine D1-or D2-like receptor mechanism. To do this, levodopa was first administered daily as an intravitreal injection or topical eye drop, at one of four ascending doses, to chicks developing LiM. Levodopa's mechanism of action was then examined by co-administration of levodopa injections with D1-like (SCH-23390) or D2-like (spiperone) dopamine antagonists in chicks developing FDM or LIM. For both experiments, levodopa's effectiveness was examined by measuring axial length and refraction after 4 days of treatment. Levodopa inhibited the development of LIM in a dose-dependent manner similar to its inhibition of fDM when administered via intravitreal injections or topical eye drops. in both fDM and LiM, levodopa injections remained protective against myopia when co-administered with ScH-23390, but not spiperone, indicating that levodopa elicits its protection through a dopamine D2-like receptor mechanism in both paradigms. Abbreviations DOPAC 3,4-Dihydroxyphenylacetic acid FDM Form-deprivation myopia LC-MS-MS High performance liquid chromatography-tandem mass spectrometry LIM Lens induced myopia PBS Phosphate buffered saline Myopia, commonly known as short-sightedness, is a refractive disorder arising from a mismatch between the axial length and optical power of the eye. This is generally due to excessive elongation of the eye during development and into early adulthood. In urban East and Southeast Asia the prevalence of myopia in young adults has risen from 20-30% to 80-85% in the last five decades (For review see 1). The prevalence of high myopia (≤ − 6 diopters (D)) has increased disproportionately to that of myopia in the last five decades, rising from 1-5% to 10-20% (For review see 1). Although the refractive error associated with this condition can easily be corrected, such corrections do not address the sight-threatening pathologies associated with myopia, and especially high myopia, which include retinal detachment, myopic macular degeneration, staphyloma, glaucoma, and cataracts 2-6. Furthermore, the odds of such pathologies significantly increase with the severity of myopia 7. Through work in animal models, changes in retinal dopamine release have been heavily implicated in the development of myopia (for review see 8-10). Specifically, in chicks, rhesus monkeys, guinea pigs, tree shrews and in some cases mice, retinal levels of dopamine, and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), have been shown to be significantly down-regulated during the development of form-deprivation myopia (FDM) 11-16. Consistent with a role fo...

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Section: Introductionmentioning

confidence: 99%

Levodopa inhibits the development of lens-induced myopia in chicks

Thomson

Morgan

Karouta

et al. 2020

Sci Rep

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“… 5 , 13 , 15 , 16 , 20 , 29 , 36 Similarly, we have previously reported that the ability of the dopamine precursor levodopa to inhibit both forms of experimental myopia can also be blocked by the coadministration of spiperone. 24 Finally, the ability of bright-light exposure, which increases retinal dopamine levels, 48 – 51 to inhibit the development of both forms of experimental myopia can similarly be blocked by the administration of spiperone in chicks 29 (Karouta C, et al IOVS 2018;59:ARVO E-Abstract 676). Together, the majority of evidence would suggest, at least in chicks, that stimulation of the D2-like receptors underlies the ability of dopamine to inhibit the development of both forms of experimental myopia.…”

Section: Discussionmentioning

confidence: 99%

“…5,13,15,16,20,29,36 Similarly, we have previously reported that the ability of the dopamine precursor levodopa to inhibit both forms of experimental myopia can also be blocked by the coadministration of spiperone. 24 Finally, the ability of bright-light exposure, which increases retinal dopamine levels, [48][49][50][51] to inhibit the development of both forms of experimental myopia can similarly be blocked by the administration of spiperone in Table 2. Statistics denote difference of treated eyes relative to FDM or LIM only.…”

Section: Similarities In the Role Of Dopamine In Fdm And Limmentioning

confidence: 99%

Form-Deprivation and Lens-Induced Myopia Are Similarly Affected by Pharmacological Manipulation of the Dopaminergic System in Chicks

Thomson

Karouta

Ashby

2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Animal models have demonstrated a link between decreases in retinal dopamine levels and the development of form-deprivation myopia (FDM). However, the consistency of dopamine's role in the other major form of experimental myopia, that of lens-induced myopia (LIM), is less clear, raising the question as to what extent dopamine plays a role in human myopia. Therefore, to better define the role of dopamine in both forms of experimental myopia, we examined how consistent the protection afforded by dopamine and the dopamine agonist 6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol hydrobromide (ADTN) is between FDM and LIM. METHODS. Intravitreal injections of dopamine (0.002, 0.015, 0.150, 1.500 μmol) or ADTN (0.001, 0.010, 0.100, 1.000 μmol) were administered daily to chicks developing FDM or LIM. Axial length and refraction were measured following 4 days of treatment. To determine the receptor subtype by which dopamine and ADTN inhibit FDM and LIM, both compounds were coadministered with either the dopamine D2-like antagonist spiperone (0.005 μmol) or the D1-like antagonist SCH-23390 (0.005 μmol). RESULTS. Intravitreal administration of dopamine or ADTN inhibited the development of FDM (ED 50 = 0.003 μmol and ED 50 = 0.011 μmol, respectively) and LIM (ED 50 = 0.002 μmol and ED 50 = 0.010 μmol, respectively) in a dose-dependent manner, with a similar degree of protection observed in both paradigms (P = 0.471 and P = 0.969, respectively). Coadministration with spiperone, but not SCH-23390, inhibited the protective effects of dopamine and ADTN against the development of both FDM (P = 0.214 and P = 0.138, respectively) and LIM (P = 0.116 and P = 0.100, respectively). CONCLUSIONS. pharmacological targeting of the retinal dopamine system inhibits FDM and LIM in a similar dose-dependent manner through a D2-like mechanism.

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“…At that time, paralysis of accommodation was considered as a major mechanism by which atropine inhibits myopia, but this view has changed after it was found that atropine inhibits myopia also in avian models which have ciliary muscles not sensitive to atropine [17]. At present, the following mechanisms are discussed: (1) atropine stimulating dopamine release from the retina [18,19] which represents an inhibitory signal for eye growth and myopia progression (review [20]), (2) atropine partially antagonizing adrenergic transmission by acting on alpha-2a receptors, in addition to muscarinic receptors [21], (3) atropine stimulating EGR-1 which is considered a growth-inhibiting signal for the eye [22,23], (4) atropine causing choroidal thickening by relaxing non-vascular smooth muscles and/or stimulating choroidal blood flow [24], (5) a direct inhibitory effect of atropine on scleral growth [25,26].…”

Section: Introductionmentioning

confidence: 99%

A retrospective analysis of the therapeutic effects of 0.01% atropine on axial length growth in children in a real-life clinical setting

Kaymak

Graff

Schaeffel

et al. 2021

Graefes Arch Clin Exp Ophthalmol

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Background Several randomized controlled studies have demonstrated the beneficial effects of 0.01% atropine eye drops on myopia progression in children. However, treatment effects may be different in a routine clinical setting. We performed a retrospective analysis of our clinical data from children to investigate the effect of 0.01% atropine eye drops on myopia progression in a routine clinical setting. Methods Atropine-treated children were asked to instill one drop of 0.01% atropine in each eye every evening at 5 days a week. Myopic children who did not undergo atropine treatment served as controls. Objective refraction and ocular biometry of 80 atropine-treated and 103 untreated children at initial visit and 1 year later were retrospectively analyzed. Results Myopic refractions in the treated and untreated children at initial visit ranged from −0.625 to −15.25 D (−4.21 ± 2.90 D) and from −0.125 to −9.375 D (−2.92 ± 1.77 D), respectively. Ages at initial visit ranged from 3.2 to 15.5 years (10.1 ± 2.7 years) in the treated and from 3.4 to 15.5 years (11.2 ± 3.0 years) in untreated children. Two-factor ANOVA for age and atropine effects on axial length growth confirmed that axial length growth rates declined with age (p<0.0001) and revealed a significant inhibitory effect of atropine on axial length growth (p<0.0015). The atropine effect on axial length growth averaged to 0.08 mm (28%) inhibition per year. Effects on refraction were not statistically significant. Conclusion The observed atropine effects were not very distinctive: Statistical analysis confirmed that atropine reduced axial length growth, but to an extent of minor clinical relevance. It was also shown that beneficial effects of 0.01% atropine may not be obvious in each single case, which should be communicated with parents and resident ophthalmologists.

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Studies on retinal mechanisms possibly related to myopia inhibition by atropine in the chicken

Cited by 32 publications

References 72 publications

Levodopa inhibits the development of lens-induced myopia in chicks

Levodopa inhibits the development of lens-induced myopia in chicks

Form-Deprivation and Lens-Induced Myopia Are Similarly Affected by Pharmacological Manipulation of the Dopaminergic System in Chicks

A retrospective analysis of the therapeutic effects of 0.01% atropine on axial length growth in children in a real-life clinical setting

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