cAMP Level Modulates Scleral Collagen Remodeling, a Critical Step in the Development of Myopia

作者：Yijin Tao, Miaozhen Pan, Shufeng Liu, Fang Fang, Runxia Lu, Chanyi Lu, Min Zheng, Jianhong An, Hongjia Xu, Fuxin Zhao, Jiang‐Fan Chen, Jia Qu, Xiangtian Zhou · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0071441 · 被引用次数：53 · 研究领域：Glaucoma and retinal disorders、Corneal surgery and disorders、Ophthalmology and Visual Impairment Studies

The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC) activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.