Genome-wide analysis of retinal transcriptome reveals common genetic network underlying perception of contrast and optical defocus detection

Refractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina. Here, we used genome-wide RNA-sequencing (RNA-seq) to conduct analysis of the retinal genetic networks underlying contrast perception and refractive eye development. We report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus. Together, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development. Analysis of RNA expression in the retina of 129S1/svlmj, A/J, C57BL/6J, CAST/EiJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ mice屈光眼发育在正视化（emmetropization）过程中受光学离焦调控。长期过度暴露于负光学离焦环境易诱发近视。然而目前学界对视网膜如何感知光学离焦仍缺乏系统性认知。本研究采用全基因组RNA测序（RNA-seq）技术，针对对比度感知与屈光眼发育背后的视网膜遗传调控网络开展分析。研究发现，介导对比度感知的遗传调控网络在光学离焦感知与正视化过程中发挥关键作用。结果表明，对比度感知、视网膜生物钟通路与光学离焦感知相关信号通路三者间存在相互调控关系。本研究还观察到，绝大多数与人类近视相关的基因均参与光学离焦信号的处理过程。综上，本研究结果支持“视网膜以对比度作为替代标志物感知光学离焦”这一假说，并为屈光眼发育的分子信号调控机制提供了全新的研究视角。本研究针对129S1/svlmj、A/J、C57BL/6J、CAST/EiJ、NOD/ShiLtJ、NZO/HlLtJ、PWK/PhJ及WSB/EiJ品系小鼠的视网膜开展了RNA表达水平分析。