Effects of Dopaminergic Agents on Progression of Naturally Occurring Myopia in Albino Guinea Pigs (<i>Cavia porcellus</i>)

Jiang, Liqin; Long, Keli; Schaeffel, Frank; Zhou, Xiangtian; Zheng, Yibo; Ying, Huangfang; Liu, Fan; Stell, William K.; Qu, Jia

doi:10.1167/iovs.14-14294

Cited by 54 publications

(48 citation statements)

References 51 publications

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“…Non-specific DA receptor agonists (L-DOPA and APO) produce more consistent and effective inhibition of myopia development than D1-like and D2-like DA agonists, suggesting that the interaction between DA D1-like and D2-like receptors might be important. Furthermore, bi-phasic effects have been reported for APO and the D2-like agonist quinpirole on control of myopia: high doses of APO inhibit FDM, while low doses promote FDM in guinea pigs (Jiang et al, 2014b); in contrast, quinpirole inhibits myopia at low doses and promotes myopia at high doses in C57 mice (Zhou, unpublished data); while both effects are abolished in D 2 R KO mice (Zhou, unpublished data). This suggests that two distinct elements of DA receptor actions may exist with opposite effects under varying DA concentrations (Figure 1).…”

Section: Challenges In Understanding the Role Of Da Signaling In Mmentioning

confidence: 94%

“…There are also examples of decreased DA due to genetic defects. For example, in albino guinea pigs with defective tyrosine metabolism (Hansson et al, 1980), serum DOPA levels are markedly reduced, which may lead to spontaneous myopia and the altered response to FDM (Jiang et al, 2011; Jiang et al, 2014b). Additionally, administration of 6-OHDA in wild-type mice results in relative myopic refractive errors under normal visual conditions and enhanced FDM response (Wu et al, 2016).…”

Section: Effects Of Altered Da Levels On Myopic Eye Growthmentioning

confidence: 99%

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Dopamine signaling and myopia development: What are the key challenges

Zhou

Pardue

Iuvone

et al. 2017

Progress in Retinal and Eye Research

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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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Section: Challenges In Understanding the Role Of Da Signaling In Mmentioning

confidence: 94%

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

Self Cite

244

203

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“…53 Nonetheless, the conclusion from results in mice that myopia development is promoted by D2R activation and inhibited by D1R activation is largely supported by findings from guinea pigs (Zhou X, et al IOVS 2013;54:ARVO E-Abstract 3678). 29 The action of APO, which binds efficiently to D1-and D2-like receptors, depends on the local concentration, the endogenous retinal dopamine level (especially the extracellular dopamine level), and the active status of the dopamine receptors. 54 Obviously, differences in routes of drug administration (intravitreal injection in chickens and intraperitoneal injection in our study) lead to different drug distributions within the retina.…”

Section: D1r-dependent Mechanism Of Apomorphine In Myopiamentioning

confidence: 99%

“…28 The latter finding is also supported by the observation that myopia development is inhibited by D2R antagonists in albino guinea pigs. 29 The partial inhibition of FDM in C57BL/6 mice by APO may reflect opposing effects arising from activation of different subtypes of dopamine receptors. In contrast to D2Rs, inactivation of D1Rs by the D1R antagonist SCH39166 inhibited the development of myopia in mice.…”

mentioning

confidence: 99%

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

Huang

Zhang

Wang

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To determine the roles of dopamine D2 receptors (D2Rs) and dopamine D1 receptors (D1Rs) in the inhibition of form-deprivation myopia (FDM) by the nonselective dopamine agonist apomorphine (APO) in D2R-knockout (D2R-KO) and D1R-KO mice. METHODS.Retinal layer thicknesses and electroretinograms (ERGs) were analyzed in KO mice and in D2R and D1R antagonist-treated mice. D2R-KO or D1R-KO mice and wild-type (WT) littermates were subjected to form deprivation during postnatal weeks 5 to 8. Both groups were intraperitoneally injected daily with either APO (5 lg/g body weight) dissolved in 1 lg/ lL ascorbic acid or vehicle alone. Refraction, vitreous chamber depth (VCD), and axial length (AL), among other parameters, were measured prior to and at the end of the treatment period.RESULTS. The retinal layer thicknesses and ERGs in KO mice were similar to those treated with D2R and D1R antagonists. APO administration in WT mice inhibited the development of FDM by approximately 80%. FDM in D2R-KO mice was inhibited approximately 50% compared with WT mice and was further inhibited by APO to a level similar to that in APO-treated WT mice. FDM development in D1R-KO mice was similar to that in WT mice and was not affected by APO administration. The changes in VCD and AL were consistent with refraction data.CONCLUSIONS. In mice, APO-mediated FDM inhibition was abolished by D1R KO but not D2R KO. This indicates the specificity of D1Rs for the pharmacologic inhibitory effect of APO on FDM and a nonessential role of D2Rs in this process in mice.

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“…29 Similarly, a D1R antagonist SCH23390 enhanced progression of naturally occurring myopia while a D1R agonist SKF38393 inhibited it in albino guinea pigs. 30 Moreover, preliminary studies indicate that D1R-like agonists inhibit FDM while D1R-like antagonists enhance FDM in C57BL/6 mice. These results support the notion of D1R involvement in myopia development at least in chicks, mice, and guinea pigs.…”

mentioning

confidence: 99%

Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina

Chen

Zhi

Ruan

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Chen S, Zhi Z, Ruan Q, et al. Bright light suppresses form-deprivation myopia development with activation of dopamine D1 receptor signaling in the ON pathway in retina. Invest Ophthalmol Vis Sci. 2017;58:230658: -231658: . DOI:10.1167 PURPOSE. To determine whether dopamine receptor D1 (D1R) signaling pathway activation by bright light (BL) in specific retinal neuronal cell types contributes to inhibiting formdeprivation myopia (FDM) in mice.METHODS. Mice (3-weeks old) were raised under either normal light (NL: 100-200 lux) or BL (2500-5000 lux) conditions with or without form deprivation. Refraction changes were evaluated with an eccentric infrared photorefractor, and ocular axial components with optical coherence tomography. The D1R antagonist, SCH39166, was intraperitoneally injected daily to evaluate if BL mediates declines in FDM development through D1R activation. Six different biomarkers of retinal neuronal types delineated differential distribution of D1R expression. cFos and phosphorylated tyrosine hydroxylase (p-TH) immunofluorescent staining evaluated D1R receptor activation and dopamine synthesis, respectively. CONCLUSIONS. Bright light increases D1R activity in the BCs of the ON pathway, which is associated with less myopic shift and ocular elongation than those occurring in NL. These declines suggest that increased D1R activity in the ON pathway contributes to the BL suppression of FDM development in mice.

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Effects of Dopaminergic Agents on Progression of Naturally Occurring Myopia in Albino Guinea Pigs (Cavia porcellus)

Cited by 54 publications

References 51 publications

Dopamine signaling and myopia development: What are the key challenges

Dopamine signaling and myopia development: What are the key challenges

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

Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina

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