Establishment and measurement of myopia in mice with ON‐bipolar cell defects

Abstract

AbstractPurpose: Myopia is a multifactorial eye disorder caused by genetic and environmental factors and is inhibited by light exposure. Complete congenital stationary night blindness (cCSNB) a group of genetically and clinically heterogeneous retinal disorders associated with high myopia in patients. Mutations in cCSNB‐associated genes have been found to disrupt the transmission of ON‐bipolar cells (ON‐BC) in the retina. As ON‐BCs are responsible for the retinal integration of the perception of surrounding light intensity, which is disrupted in myopia, we seek to determine whether cCSNBs models are more susceptible to develop myopia.Methods: We evaluated the levels of retinal Dopamine (DOPA) and its metabolite 3,4‐Dihydroxyphenylacetic acid (DOPAC), commonly used markers of myopia, in three cCSNB mouse models lacking Grm6, Gpr179 or Lrit3. Using an eccentric infrared photorefractometer, we measured the refractive development of two cCSNB mouse models lacking Gpr179 or Lrit3. To assess the sensitivity of cCSNB mouse lines to myopia induction, we developed a lens‐induced myopia (LIM) model and measured the induced refractive error in mice lacking Gpr179 or Lrit3.Results: Our preliminary data revealed decreased levels of both retinal DOPA and DOPAC in all tested cCSNB mouse models. All tested groups presented the same kinetic of refractive development. Mice lacking Gpr179 displayed a higher sensitivity to LIM as shown by an increase in the mean interocular shift compared to wild‐type littermates. Mice lacking Lrit3 with LIM will be measured to document the refractive errors induced by the ON‐BC defect.Conclusions: These results suggest that disruption of the ON‐BC pathway contributes to the development of myopia and that mouse models of cCSNB represent good models to study myopia. Our data strengthen the hypothesis of an impact of ON‐BC dysfunction upon the onset of myopia. These findings provide the basis for the development of pharmacological and optical therapies.