慢性局部应用拉坦前列素对形觉剥夺性近视豚鼠巩膜和筛板的影响。
Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic Guinea pigs.
机构信息
School of Optometry and Vision Science, University of California Berkeley, Berkeley, CA, United States.
School of Optometry and Vision Science, University of California Berkeley, Berkeley, CA, United States.
出版信息
Exp Eye Res. 2019 Sep;186:107740. doi: 10.1016/j.exer.2019.107740. Epub 2019 Jul 19.
The purpose of this study was to investigate the effects of latanoprost, an ocular hypotensive prostaglandin analog, on scleral collagen fibers and laminar pores in myopic guinea pigs. Young guinea pigs underwent monocular form deprivation (FD; white plastic diffusers) from 14-days of age for 10-weeks. After the first week, FD eyes also received daily topical A) latanoprost (Lat, 0.005%, n = 5) or B) artificial tears (AT; n = 5). At the end of the treatment period, animals were sacrificed, eyes enucleated and optic nerve heads (ONH) excised to include a 4 mm diameter ring of surrounding sclera for scanning electron microscopy (SEM), and an additional 6 mm ring of sclera surrounding the ONH was excised for transmission electron microscopy (TEM). For SEM, ONH samples were first immersed in 0.2M NaOH for 30 h to isolate the collagenous structures. All samples were stained with osmium tetroxide, dried through an ethanol series and finally subjected to critical point drying before imaging. Image J was used to analyze the dimensions of laminar pores (SEM images) and scleral collagen fibers (TEM images). As previously reported in a related study, latanoprost was effective in inhibiting myopia progression in FD eyes of the guinea pigs. The scleral fibers of FD myopic eyes treated with AT were smaller and more variable in cross-sectional areas compared to untreated (fellow) eyes (mean areas: 0.0059 ± 0.0013 vs. 0.0085 ± 0.002 μm; p < 0.001), consistent with scleral changes reported for human myopia. In contrast, the scleral fibers of the Lat-treated FD eyes were similar to those of fellow eyes (0.0083 ± 0.002 vs. 0.0078 ± 0.0014 μm). However, laminar pore size appeared unaffected by either the FD or drug treatments, with no significant difference found between FD eyes and their fellows, for either treatment group. That daily topical latanoprost appeared to protect against myopia-related changes in scleral collagen, rather than exaggerating them, as might be predicted from its known action on the uveoscleral extracellular matrix, lends further support its use for myopia control. In this guinea pig myopia model, the lamina cribrosa appeared unaffected.
本研究旨在探讨前列腺素类似物拉坦前列素对近视豚鼠巩膜胶原纤维和板层孔的影响。年轻的豚鼠从 14 日龄开始进行单眼形觉剥夺（FD；白色塑料扩散器），为期 10 周。在第一周后，FD 眼还每天接受局部 A）拉坦前列素（Lat，0.005%，n=5）或 B）人工泪液（AT；n=5）治疗。在治疗期末，处死动物，眼球摘出，视神经头（ONH）切除，包括直径 4mm 的巩膜环用于扫描电子显微镜（SEM），以及 ONH 周围切除 6mm 直径的巩膜环用于透射电子显微镜（TEM）。对于 SEM，首先将 ONH 样品浸泡在 0.2M NaOH 中 30h，以分离胶原结构。所有样品均用锇酸染色，通过乙醇系列干燥，最后进行临界点干燥，然后进行成像。Image J 用于分析板层孔（SEM 图像）和巩膜胶原纤维（TEM 图像）的尺寸。如之前在一项相关研究中报道的那样，拉坦前列素可有效抑制 FD 眼的近视进展。与未治疗（同眼）眼相比，用 AT 治疗的 FD 近视眼的巩膜纤维在横截面积上更小且更不均匀（平均面积：0.0059±0.0013 vs. 0.0085±0.002μm；p<0.001），与人类近视报告的巩膜变化一致。相比之下，Lat 治疗的 FD 眼的巩膜纤维与同眼相似（0.0083±0.002 vs. 0.0078±0.0014μm）。然而，无论是 FD 还是药物治疗都似乎不会影响板层孔大小，在 FD 眼与同眼之间，无论是哪种治疗组，都没有发现显著差异。每日局部使用拉坦前列素似乎可以防止巩膜胶原与近视相关的变化，而不是像其已知的对葡萄膜巩膜细胞外基质的作用那样加剧这些变化，这进一步支持其用于近视控制。在这种豚鼠近视模型中，筛板似乎不受影响。
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