Measurement of Refractive State and Deprivation Myopia in Two Strains of Mice

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.

Section: Form Deprivationmentioning

confidence: 99%

Section: Biometric Measurementsmentioning

confidence: 99%

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

Huang

Zhang

Wang

et al. 2018

“…The refractive state was measured by an automated infrared photorefractor in a dark environment as described previously. 33,34 Refractive error values were recorded with a custom software designed by Frank Schaeffel. For each eye, an average of 50 to 100 measurements were used for analysis.…”

Section: Form-deprivation Myopia Modelmentioning

confidence: 99%

The Role of the RhoA/ROCK Signaling Pathway in Mechanical Strain-Induced Scleral Myofibroblast Differentiation

Yuan

et al. 2018

PURPOSE. Biomechanical properties changes and a-smooth muscle actin (a-SMA) overexpression are involved in myopia scleral remodeling. However, interactions between altered tissue biomechanics and cellular signaling that sustain scleral remodeling have not been well defined. We determine the mechanisms of mechanotransduction in the regulation of a-SMA expression during myopia scleral remodeling.METHODS. Guinea pigs were used to establish a form-deprivation myopia (FDM) model. Protein profiles in myopic sclera were examined using tandem mass spectrometry. Ras homolog gene family member A (RhoA) and a-SMA expressions were confirmed using quantitative (q) RT-PCR and Western blotting. Scleral fibroblasts were cultured and subjected to 4% cyclic strain. Levels of RhoA, rho-associated protein kinase-2 (ROCK2), myocardin-related transcription factor-A (MRTF-A), serum response factor (SRF), and a-SMA were determined by qRT-PCR and Western blotting in groups with or without the RhoA siRNA or ROCK inhibitor Y27632. MRTF-A and a-SMA were evaluated by confocal immunofluorescent microscopy and myofibroblasts were enumerated using flow cytometry.RESULTS. mRNA and protein levels of RhoA and a-SMA were significantly increased in the FDM eyes after 4 weeks of form-deprivation treatment. The 4% static strain increased expressions of RhoA, ROCK2, MRTF-A, SRF, and a-SMA as well as nuclear translocalization of MRTF-A in scleral fibroblasts compared to those without strain stimulation. Additionally, the percentage of myofibroblasts increased after strain stimulation. Conversely, inhibition of RhoA or ROCK2 reversed the strain-induced a-SMA expression and myofibroblast ratio.CONCLUSIONS. Mechanical strain activated RhoA signaling and scleral myofibroblast differentiation. Strain also mediated myofibroblast differentiation via the RhoA/ROCK2-MRTF-A/SRF pathway. These findings provided evidence for a mechanical strain-induced RhoA/ROCK2 pathway that may contribute to myopia scleral remodeling.

“…Form-deprivation myopia was induced by the placement of a translucent occluder onto a randomly selected eye for 4 weeks, as described previously by Schaeffel et al 36 D1R antagonist, SCH39166 solution (0.04 lg/lL; Tocris bioscience, Glasgow, UK) was freshly prepared by dissolving it in dimethyl sulfoxide (DMSO; 0.11 lg/lL; Sigma, Buchs, Switzerland). SCH39166 (0.4 lg/g body weight), or DMSO (1.1 lg/g bodyweight) were intraperitoneally injected daily without anesthesia to drug-injection groups.…”

Section: Induction Of Fdm and Drug Administrationmentioning

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

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.