Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia

Abstract

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^-/- mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.

Keywords: CSNB; GPR179; ON-bipolar cells; dopamine; myopia; refractometry.

Figure 1

Retinal levels of DA and DOPAC. Quantification of DA (A), DOPAC (B) and the DOPAC/DA ratio (C) in light-adapted adult Gpr179^+/+ and Gpr179^−/− retinas. Data are expressed as Mean ± SEM. ns: not significant, **: p ≤ 0.01, ***: p < 0.001.

Figure 2

Natural refractive development. Measurement of the refractive state of Gpr179^+/+ and Gpr179^−/− mice across age. Data are expressed as Mean ± SEM.

Figure 3

Lens-induction of myopia. Measurement of the kinetics of mean interocular shift between the goggled and ungoggled eyes of Gpr179^+/+ and Gpr179^−/− mice. Data are expressed as Mean ± SEM. **: p ≤ 0.01, ***: p < 0.001.