Amphiregulin and ocular axial length

Amphiregulin and ocular axial length
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双调蛋白和眼轴长度

DOI:
10.1111/aos.14080
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发表时间:
2019-05-01
影响因子:
3.4
通讯作者:
Jonas, Jost B.
Jonas, Jost B.
中科院分区:
医学3区
文献类型:
--
作者:
Dong, Li;Shi, Xu Han;Jonas, Jost B.

文献摘要

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目的探讨双调蛋白作为信使分子在眼轴延长中的作用。方法实验研究采用豚鼠(总计n = 78)(年龄:3-4周),其经历了双侧晶状体诱导的近视化,并在15天后以每周间隔接受三次眼内注射双调蛋白抗体(剂量:5 μ g、10 μ g、20 μ g)右眼注射,左眼注射三次磷酸盐缓冲盐水;以及没有晶状体诱导近视的豚鼠,其接受了三次单侧眼内注射双调蛋白抗体(剂量:20 μ g)或双调蛋白(剂量:1 ng; 10 ng; 20 ng)注射到他们的右眼中,并且三次磷酸盐缓冲盐水注射到他们的左眼中。7天后,处死动物。在活体内,我们进行了生物统计学,组织学和免疫组织化学死后。结果在双侧晶状体诱导的近视动物中,接受双调蛋白抗体的右眼显示出剂量依赖性的轴向延长减少(剂量:5 μ g:侧差:0.14 ± 0.05 mm;10 μ g:0.22 ± 0.06 mm; 20 μ g:0.32 ± 0.06 mm; p < 0.001)、巩膜增厚(均p < 0.05)以及视网膜核层和视网膜色素上皮(RPE)中较高的细胞密度(均p < 0.05)。在没有晶状体诱导近视的动物中,应用双调蛋白抗体(20 μ g)的右眼显示出轴向伸长减少(p = 0.04),并且注射双调蛋白的右眼经历了增加的(p = 0.02)轴向伸长呈剂量依赖性(1 ng:0.04 +/- 0.06 mm; 10 ng:0.10 +/- 0.05 mm; 20 ng:0.11 +/- 0.06 mm)。与没有透镜诱导的轴向伸长的眼睛相比,具有透镜诱导的轴向伸长的眼睛揭示了在免疫组织化学和内源性双调蛋白和表皮生长因子受体的mRNA的更高表达后双调蛋白的增加的可视化,特别是在视网膜内核层的外部和在RPE中。结论双调蛋白可能与幼年豚鼠眼轴延长有关。
Purpose To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation. Methods The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 mu g, 10 mu g, 20 mu g) into their right eyes, and three phosphate-buffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 mu g) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem. Results In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 mu g: side difference: 0.14 +/- 0.05 mm;10 mu g: 0.22 +/- 0.06 mm; 20 mu g: 0.32 +/- 0.06 mm; p < 0.001), thicker sclera (all p < 0.05) and higher cell density in the retinal nuclear layers and retinal pigment epithelium (RPE) (all p < 0.05). In animals without lens-induced myopia, the right eyes with amphiregulin antibody application (20 mu g) showed reduced axial elongation (p = 0.04), and the right eyes with amphiregulin injections experienced increased (p = 0.02) axial elongation in a dose-dependent manner (1 ng: 0.04 +/- 0.06 mm; 10 ng: 0.10 +/- 0.05 mm; 20 ng: 0.11 +/- 0.06 mm). Eyes with lens-induced axial elongation as compared to eyes without lens-induced axial elongation revealed an increased visualization of amphiregulin upon immunohistochemistry and higher expression of mRNA of endogenous amphiregulin and epidermal growth factor receptor, in particular in the outer part of the retinal inner nuclear layer and in the RPE. Conclusion Amphiregulin may be associated with axial elongation in young guinea pigs.