短波长蓝光干预豚鼠实验性近视进展的作用及机制研究

Myopia is one of the most common diseases which cause visual disturbance, and its prevalence increases quickly in Chinese teenagers. Now there are no big achievements on prevention and cure of myopia and research of its mechanism all over the world. Recently, more and more attentions are paid to the effect of chromatic signals on myopia development. Our group has taken the lead to launch investigations on the effect of different monochromatic lights to refractive development in guinea pigs and Rhesus monkeys. The results showed that long-wavelength light can induce myopia and short-wavelength light can inhibit normal elongation of vitreous body in animal eyes. Now we will further investigate whether the short-wavelength light can block the development of myopia on the basis of our finished research. We will use the short-wavelength light to interfere in the defocus-induced myopia in guinea pigs and observe the effect of the light. Moreover, the mechanism of this course will be studied through many investigative procedures, including the distribution, density, quantity and ultra structure of the retinal cones, expression of different opsins, Egr-1, MMP-2 and TIMP-2, content of retinoic acid, dry weight of posterior sclera, etc.. This research is a further study on the basis of the key project of NSFC. It will make it clear what and how the short-wavelength light interferes in the myopia, and may offer novel way to prevent myopia.

近视是最常见引起视力障碍的眼病，患病率逐年上升，在近视防治及发生机制研究上没有更多突破是重要原因。近年来色觉信号在近视形成中的作用逐渐受到国内外关注。我们在国内外率先开展不同色光对豚鼠和恒河猴屈光发育作用研究，研究显示长波长红光可诱导近视形成，而短波长蓝光能抑制正常眼球玻璃体腔的延长。在此基础上本课题将进一步研究短波长蓝光对进展中的近视是否有干预作用。我们欲将短波长蓝光作用于豚鼠光学离焦诱导的近视模型上，通过观察屈光度、眼轴等指标明确其对近视的干预作用。通过观察视网膜上接收色觉信号的视锥细胞的分布、数量、超微结构，检测不同视蛋白表达，视黄酸、Egr-1表达，后巩膜干重，巩膜胶原重塑最重要的酶MMP-2和TIMP-2表达，研究其对近视干预的作用机制。本研究是国家自然科学基金重点项目的进一步研究,将明确短波长蓝光干预近视的作用及机制，有望为近视预防和控制提供新的途径。

我们前期对豚鼠和恒河猴屈光发育研究显示：长波长光可诱导近视形成，而短波长光能抑制正常眼球玻璃体腔的延长。在此基础上本课题研究了短波长光对进展中近视的干预作用。我们将2周龄豚鼠随机分成430nm短波长蓝光组（SL组）和白光组（BL组）。两组右眼均配戴－5.00D 镜片，左眼为自身对照。SL组置于430nm蓝光中进行饲养，BL组置于正常白光环境下饲养。实验前进行眼球的生物学测量（屈光度，角膜曲率，眼轴各部分长度），实验开始后每2周重复测量以上数据，持续观察时间为8周。同时通过观察视网膜上接收色觉信号的视锥细胞的分布、数量，检测视网膜不同视蛋白、巩膜MMP-2、TIMP-2及胶原的表达，以及脉络膜视黄酸相关受体（RAR-β）的表达，初步探究430nm单色光对近视干预的作用机制。. 实验开始后，SL组和BL组右眼屈光度均开始下降，至实验结束时SL组右眼较BL组右眼偏远视约1.20D（p<0.05）。SL组右眼玻璃体腔长度较实验开始时延长0.01mm，而BL组右眼玻璃体腔长度较实验开始时延长0.18mm，两组比较差异有统计学意义（p<0.05）。眼球HE染色发现SL组右眼后极部巩膜相对于BL组明显增厚。视网膜铺片结果提示和BL组比较，SL组右眼S视锥细胞数量增多而M视锥细胞数量减少。Western blot 示SL组M视蛋白表达明显降低，脉络膜RAR-β表达明显降低，巩膜中TIMP-2表达明显升高。RT-PCR示巩膜Ⅰ型胶原的表达明显升高。研究结果提示，430nm单色光对豚鼠光学离焦性近视有阻滞作用。短波长光干预近视进展的机制可能通过改变视锥细胞的数量及类型并激活相关通路实现，视黄酸相关通路可能在短波长光干预近视进展中发挥重要作用。