内在光感受性视网膜神经节细胞（ipRGCs）在日节律光协同化影响屈光发育过程中的作用机制研究

儿童近视的发生发展机制尚不清楚，防治措施有限。我们近期发现增加儿童户外时间和睡眠时间均可使眼轴长度更短、近视度数更低；持续光照发育期大鼠可使包含黑视素的光感受性视网膜神经节细胞（ipRGCs）数量增加，且维持小鼠正常昼夜节律需要功能完整的ipRGCs。据此提出假说：光照和昼夜节律失调可刺激ipRGCs及黑视素表达，局部影响视网膜生物钟，上行作用于视交叉上核（SCN）并反馈于视网膜，调控屈光发育过程。本项目将探讨不同强度光照对发育期小鼠ipRGCs及黑视素、昼夜节律基因、多巴胺和褪黑素的影响，明确ipRGCs在光照影响近视过程中的作用和机制；建立小鼠形觉剥夺性近视模型，探讨ipRGCs在昼夜节律失调下对近视的影响和机制；阻断ipRGCs不同亚型、上调黑视素，探讨SCN节律功能及视网膜生物钟的变化，以期阐明ipRGCs在日节律光协同化影响屈光发育过程中的作用和机制，为近视防治寻找新的理论依据。

The mechanism of myopia in children is not clear, and the prevention and treatment measures are limited. We recently found that increased outdoor time and sleep time in children resulted in shorter axial length and lower myopia. Continuous illumination increased the number of intrinsically photosensitive retinal ganglion cells (ipRGCs) containing melanopsin in developing rats, and fully functional ipRGCs were required to maintain normal circadian rhythms in mice. It is therefore hypothesized that light and circadian rhythm dysregulation can stimulate the expression of ipRGCs and melanopsin, locally affecting retinal biological clock, upstream action on the suprachiasmatic nucleus (SCN) and feed back to the retina to regulate the process of refractive development. In this project, the effects of different intensities of light on ipRGCs, melanopsin, circadian rhythm genes, dopamine and melatonin in developing mice will be firstly investigated to clarify the role and mechanism of ipRGCs in the process of light affecting myopia. A mouse model of form-deprivation myopia will be established to investigate the effect and mechanism of ipRGCs on myopia under circadian rhythm disorder. Blocking different subtypes of ipRGCs, upregulating melanopsin, and exploring the changes of SCN rhythm function and retinal biological clock, in order to elucidate the role and mechanism of ipRGCs in the process of diurnal rhythm light synergism affecting the development of refraction, and to find a new theoretical basis for the prevention and treatment of myopia.