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.

近视是最常见的眼部疾病，由异质遗传和环境因素引起。罕见的进行性和静止性遗传性视网膜疾病通常与高度近视有关。与近视有关的基因编码的蛋白质参与多种生物过程，包括眼睛形态发生、细胞外基质组织、视觉感知、昼夜节律和视网膜信号传导。在模仿近视的动物模型中发现的差异表达基因 (DEG) 有助于提出与人类近视有关​​的候选基因。人类和动物模型中的完全先天性静止性夜盲症 (cCSNB) 代表 ON-双极细胞信号传输缺陷，也与高度近视有关。因此，它也代表了一个有趣的模型来识别近视相关基因以及疾病机制。虽然夜盲症的起源在分子上已经确定，但需要进一步的研究来阐明 cCSNB 患者近视发展的机制。在三种不同的 cCSNB 小鼠模型上使用全转录组分析（在Gpr179 ^−/−、Lrit3 ^−/−和Grm6 ^−/− )，我们确定了视网膜信号级联的新参与者，它们也是近视的新候选基因。我们的转录组数据与已发表的转录组数据库和近视病例的全基因组关联研究的荟萃分析使我们提出了新的生物/细胞过程/机制，这些过程可能是 cCSNB 受试者近视的起源。该结果为指导药物近视疗法的发展提供了基础。