Shedding light on myopia by studying complete congenital stationary night blindness

Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare progressive and stationary inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in a variety of biological processes including eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signaling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON-bipolar cell signal transmission defect and is also associated with high myopia. Thus, it represents also an interesting model to identify myopia-related genes, as well as disease mechanisms. While the origin of night blindness is molecularly well established, further research is needed to elucidate the mechanisms of myopia development in subjects with cCSNB. Using whole transcriptome analysis on three different mouse models of cCSNB (in Gpr179-/-, Lrit3-/- and Grm6-/-), we identified novel actors of the retinal signaling cascade, which are also novel candidate genes for myopia. Meta-analysis of our transcriptomic data with published transcriptomic databases and genome-wide association studies from myopia cases led us to propose new biological/ cellular processes/mechanisms potentially at the origin of myopia in cCSNB subjects. The results provide a foundation to guide the development of pharmacological myopia therapies.

Automated summary

Myopia is a common eye disorder caused by genetic and environmental factors. High myopia is often associated with rare inherited retinal disorders. Genes involved in myopia are related to various biological processes, including eye development, matrix organization, visual perception, circadian rhythms, and retinal signaling. Animal models mimicking myopia can help identify candidate genes implicated in human myopia. Complete congenital stationary night blindness represents an interesting model for studying myopia and retinal signaling defects. Transcriptome analysis in mouse models of cCSNB identified new candidate genes for myopia. Integration of transcriptomic data and genome-wide association studies provides insights into the potential mechanisms underlying myopia development in cCSNB subjects. These findings have implications for the development of pharmacological therapies for myopia.