Abstract
Purpose :
High myopia is a major risk factor for blinding ophthalmic diseases, yet the genes and mechanisms that give rise to it are poorly understood. Complete congenital stationary night blindness (cCSNB) is caused by mutations in genes expressed in ON-bipolar cells and is strongly correlated with high myopia. To gain insight into molecular mechanisms of myopia, whole transcriptome sequencing (RNA-seq) was performed on three mouse models of cCNSB (Zeitz et al. Prog Ret Eye Res. 2023). Prkca, which encodes PKCα, a marker of rod bipolar cells, was found to be differentially expressed in all three cCSNB models. While Prkca has not been previously shown to be associated with high myopia, because of its differential upregulation, we hypothesized that Prkca knockout mice would have reduced levels of retinal dopamine and an increased susceptibility to lens-induced myopia (LIM).
Methods :
Prkca +/+ and Prkca-/- mice were used in this study. Retinal levels of dopamine and its metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) were measured using ultra performance liquid chromatography. Myopia was induced by placing a -25 D lens in front of the right eye of 3-week-old mice for 3 weeks (lens-induced myopia, LIM). Refractive development and LIM optic shift were measured using an infrared photorefractor, as developed by Frank Schaeffel (Optom Vis Sci. 2004). Full field electroretinograms (ERGs) were performed on both LIM and control eyes in wild type and Prkca-/- mice. Oscillatory potentials (OPs) were obtained by 30-150 Hz bandpass filtering.
Results :
Dopamine and DOPAC levels were reduced in Prkca-/- mice compared to wild type. Refraction measurements in 3- and 4-week-old untreated mice revealed that Prkca-/- eyes were myopic compared to wild type eyes, but recovered and were similar and slightly hyperopic at 6 weeks of age and older. After 3 weeks of LIM, preliminary data showed a larger myopic shift in Prkca-/- eyes compared to wild type. ERG a- and b-waves were not significantly different between LIM and control eyes. Normalized to the b-wave, OPs appear to be larger in recordings from LIM eyes, compared to control.
Conclusions :
Our results indicate that PKCα, which is abundantly expressed in rod bipolar cells, may be important for emmetropization. This further reinforces the contribution of the retinal ON pathway in regulating axial growth of the eye.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.