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Han na Park, Christopher Tan, Jacob Light, Fazila Aseem, P Iuvone, Machelle Pardue; Refractive Development and Form-Deprivation in Dopamine D4 Receptor Knock-Out Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5167.
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© ARVO (1962-2015); The Authors (2016-present)
Dopamine has been implicated in the regulation of ocular growth and development of myopia. Furthermore, recent studies have shown that dopamine receptors have selective effects on contrast sensitivity and visual acuity. Here, we explore the contribution of dopamine D4 receptors (D4) in refractive development and its possible environmental interactions during form-deprivation.
Refractive development of D4 knock-out (KO) and age-matched C57BL/6 wild-type (WT) mice were monitored from postnatal day (P) 28 to 112. Biweekly measurements of refractive error were made with a photorefractor and corneal radius of curvature (CRC) with keratometry. Ocular parameters were measured using cross-sectional images from 1310nm SD-OCT, including corneal thickness (CT), anterior chamber depth (ACD), posterior chamber depth (PCD), lens thickness (LT), retinal thickness (RT), and axial length (AL). A separate cohort of D4 KO mice received head-mounted diffuser goggles over the right eye at P28 to induce FD myopia. These mice were measured with the same instruments listed above. At end of the experiment, retinas were collected for quantification of dopamine using HPLC.
The D4 KO mice (n=4-13) were relatively more myopic compared to WT mice (n=14-34) with an average diopter (D) difference of -3.15±1.20 across the age range of P28 to P112, respectively (RM ANOVA, p <0.001). Across the same ages, D4 KO mice had significantly longer CRC (0.03 ±0.01mm, RM ANOVA, p=0.03) and a trend for longer axial lengths (12 ± 2µm) and thicker lenses (26 ±4µm) than WT mice. After 2 weeks of goggling, D4 KO and WT FD mice showed a significant myopic shift of ~2D compared to contralateral and naïve control eyes (RM ANOVA, main effect p=0.016 and p=0.005, respectively). Goggled D4 KO mice showed trends towards shorter CRC (14µm), longer ACD (10µm), longer PCD (31µm), and longer AL (32µm) compared to opposite and naïve eyes, while WT mice did not have measureable changes at this time point.
The absence of the D4 resulted in more myopic refractions with normal refractive development. However, the response to form deprivation was not significantly altered. At 2 weeks post-FD, the ocular parameters in D4 KO mice showed trends that correspond to the refractive changes, but did not reach significance with the current animal numbers and the resolution of the current instruments.
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