Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.
Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.
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DOI：
10.1167/iovs.09-3998
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发表时间：
2010-09
影响因子：
4.4
通讯作者：
Xiangtian Zhou;Qinzhu Huang;Jian-hong An;Runxia Lu;Xiaoyi Qin;Li-qin Jiang;Yuan Li;Jianhua Wang
中科院分区：
文献类型：
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作者：
Xiangtian Zhou;Qinzhu Huang;Jian-hong An;Runxia Lu;Xiaoyi Qin;Li-qin Jiang;Yuan Li;Jianhua Wang
目的探讨腺苷A2a受体(A2AR)在小鼠生后屈光发育中的作用。方法使用专门为小鼠设计的定制生物识别系统，通过检测A2AR基因敲除(KO)小鼠和野生型(WT)小鼠出生后28天至56天的屈光状态和生物计量学来评估相对近视的发展。采用自定义光学相干断层扫描仪(OCT)测量眼球大小，偏心红外光折射仪(EIR)测量屈光状态，改良角膜曲率计测量角膜曲率半径。术后35天取材，用电子显微镜观察巩膜胶原的直径和密度。用实时定量RT-PCR和胶原检测试剂盒检测A2AR激活对培养的人巩膜成纤维细胞胶原基因表达和可溶性胶原生成的影响。结果与WT胎相比，A2AR KO小鼠表现出相对近视(P28和P35的平均差异为5.1D)，并伴随着从P28到P56的VC深度和眼轴长度的增加。此外，A2AR KO组小鼠的近视改变与巩膜超微结构的变化有关：电子显微镜显示A2AR KO组与WT组相比，胶原纤维密度更高，直径更小。最后，A2AR激活诱导培养的人巩膜成纤维细胞表达I型、III型和V型胶原，并增加可溶性胶原的产生。结论A2AR基因缺失促进了小鼠相对近视的发生，在出生后发育过程中眼轴增加，巩膜胶原纤维结构改变。因此，A2AR可能在正常屈光发育中起重要作用。
PURPOSE To critically evaluate whether the adenosine A2A receptor (A2AR) plays a role in postnatal refractive development in mice. METHODS Custom-built biometric systems specifically designed for mice were used to assess the development of relative myopia by examining refraction and biometrics in A2AR knockout (KO) mice and wild-type (WT) littermates between postnatal days (P)28 and P56. Ocular dimensions were measured by customized optical coherence tomography (OCT), refractive state by eccentric infrared photorefraction (EIR), and corneal radius of curvature by modified keratometry. Scleral collagen diameter and density were examined by electron microscopy on P35. The effect of A2AR activation on collagen mRNA expression and on soluble collagen production was examined in cultured human scleral fibroblasts by real-time RT-PCR and a collagen assay kit. RESULTS Compared with WT littermates, the A2AR KO mice displayed relative myopia (average difference, 5.1 D between P28 and P35) and associated increases in VC depth and axial length from P28 to P56. Furthermore, the myopic shift in A2AR KO mice was associated with ultrastructural changes in the sclera: Electron microscopy revealed denser collagen fibrils with reduced diameter in A2AR KO compared with WT. Last, A2AR activation induced expression of mRNAs for collagens I, III, and V and increased production of soluble collagen in cultured human scleral fibroblasts. CONCLUSIONS Genetic deletion of the A2AR promotes development of relative myopia with increased axial length and altered scleral collagen fiber structure during postnatal development in mice. Thus, the A2AR may be important in normal refractive development.