Investigating mechanisms of myopia in mice

Pardue, Machelle T.; Stone, Richard A.; Iuvone, P. Michael

doi:10.1016/j.exer.2012.12.014

Cited by 78 publications

(95 citation statements)

References 89 publications

(180 reference statements)

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“…The small magnitude of myopic shift observed in WT mice after 2 weeks of goggling was in close agreement with previous studies (see review, Pardue et al, 2013). Importantly, we found mGluR6−/− mice to be highly susceptible to FD myopia, developing about 5.5 D of myopia in response to 2 weeks of FD (Figure 1B).…”

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confidence: 93%

“…More recent studies using various mutant mouse models have provided stronger evidence of retinal involvement in ocular refractive development (Chakraborty et al, 2014; Pardue et al, 2008; Park et al, 2013; Park et al, 2014). Mouse models ensure complete and selective blockage of a single pathway, and allow examination of the interaction between genetic background and visual environment in refractive development (Pardue et al, 2013). …”

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confidence: 99%

“…The use of FD has become a standard method to induce experimental myopia in murine eyes (see review, Pardue et al, 2013). The small magnitude of myopic shift observed in WT mice after 2 weeks of goggling was in close agreement with previous studies (see review, Pardue et al, 2013).…”

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confidence: 99%

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ON pathway mutations increase susceptibility to form-deprivation myopia

Chakraborty

Park

Hanif

et al. 2015

Experimental Eye Research

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The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6−/− mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6−/− and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6−/− mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40 ± 0.16 D, mGluR6−/−: 6.91 ± 0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of −5.57 ± 0.72 D in mGluR6−/− mice compared to −1.66 ± 0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6−/− retinas showed significantly lower DOPAC levels (111.2 ± 33.0 pg/mg) compared to their WT counterparts (197.5 ± 11.2 pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations.

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confidence: 93%

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confidence: 99%

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ON pathway mutations increase susceptibility to form-deprivation myopia

Chakraborty

Park

Hanif

et al. 2015

Experimental Eye Research

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“…57 However, mammalian models in general have eyes similar to humans with respect to structure and biochemistry, and a great deal is known about the biology and genetics, particularly of mice. Most important of all, the various available genetic KO models, which permit specific and complete inactivation of the target gene to overcome partial specificity of pharmacologic approach, are irreplaceable by other animal models for exploring the mechanisms underlying myopia development.…”

Section: D1r-dependent Mechanism Of Apomorphine In Myopiamentioning

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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“…Moreover, rod pathways and the dopaminergic system interact structurally and functionally; for instance, DA neurons synapse onto AII and A17 amacrine cells in the rod pathway, rod-driven ON pathways stimulate DA release, which in turn decrease rod function as the retina adapts to daylight function, and loss of rods results in decreased DA levels in the retina. 32,38 The mouse recently has been adopted as an experimental model for myopia, offering the ability to manipulate genes and environment (see review 39 ). The mouse eye responds with myopic shifts when exposed to FD [40][41][42][43][44][45] or negative lens defocus.…”

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confidence: 99%