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Michael A Bergen, Han na Park, Ranjay Chakraborty, Erica G Landis, Curran Sidhu, P Michael Iuvone, Machelle T Pardue; Retinal-specific Dopamine Knock-out Mice are Myopic.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2153.
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© ARVO (1962-2015); The Authors (2016-present)
Dopamine has been implicated as a stop signal for refractive eye growth based on pharmacological studies in chickens, mammals, and primates. More recently, dopamine receptor knock-out mice have been used to elucidate dopaminergic mechanisms of refractive development (Huang et al. IOVS 2014). In this study, a Cre-mediated, retinal-specific tyrosine hydroxylase knockout (KO) mouse was studied to determine the effect of eliminating retinal dopamine on refractive development and susceptibility to form deprivation (FD) myopia.
KO mice were on a C57BL/6J background and were homozygous for both the Chx10 Cre-recombinase and floxed tyrosine hydroxylase alleles. Mice were randomly assigned to two groups, one undergoing normal refractive development and the other undergoing FD. Refractive development of KO mice and age-matched C57BL/6J wild-type (WT) mice was measured every 2 weeks from post-natal day 28 (P28) to P112. Under the FD paradigm, mice received a head-mounted diffuser goggle at P28 over their right eye (OD) and were measured weekly until P77. Measurements of refractive error, corneal curvature, and ocular biometrics were obtained using an automated photorefractor, a keratometer, and a spectral-domain optical coherence tomography system, respectively.
During normal refractive development, KO mice were significantly more myopic (at P70, KO 2.74 ± 2.18 D, n=19; WT 7.08 ± 1.47 D, n=9; p < 0.01) and had significantly shorter axial lengths (at P56, KO 3.18 ± 0.01 mm; WT 3.23 ± 0.04 mm; p < 0.05) than their WT counterparts. KO mice also had significantly steeper corneas than WT mice (at P56, KO 1.42 ± 0.03 mm; WT 1.44 ± .03 mm; p < 0.05). Both WT and KO form-deprived mice showed similar magnitudes of myopic shift (difference of right and left eyes) (at P42, KO -2.29 ± 3.59 D, n=8; WT -3.85 ± 1.35 D; n=7).
Our results support the hypothesis that dopamine is a stop signal for refractive eye growth. KO mice showed greater variability in FD myopic shifts than WT mice, which may indicate varying levels of retinal dopamine depletion in this model. Future work will correlate dopamine and DOPAC levels with refractive error and ocular parameters to comprehensively examine how dopamine concentration affects refractive development
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