Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation
Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation
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发表时间：
2016-05
期刊：
影响因子：
2.2
通讯作者：
C. Boote;Joel R. Palko;T. Sorensen;A. Mohammadvali;A. Elsheikh;A. Komáromy;X. Pan;Jun Liu
中科院分区：
文献类型：
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作者：
C. Boote;Joel R. Palko;T. Sorensen;A. Mohammadvali;A. Elsheikh;A. Komáromy;X. Pan;Jun Liu
目的：我们的目的是在由ADAMTS 10突变引起的开角型青光眼犬模型中，在可检测的疾病发作之前，描述后巩膜胶原微结构的改变。方法胶原蛋白的取向，各向异性程度（优先排列的胶原蛋白的比例），和相对密度测量在0.4 mm的空间分辨率，使用同步辐射广角X射线散射。对于结构参数的统计学评价，比较ADAMTS 10突变体（受累）犬（n = 3）和年龄匹配（携带者）对照犬（n = 3）的视乳头周围和中后巩膜的区域平均值。结果对照组和病变组犬的胶原纤维取向无明显差异。所有标本的视乳头周围巩膜的特征是强烈排列的环状胶原环绕视神经乳头。受累犬中后巩膜的胶原蛋白各向异性显著降低（载体：0.27±0.11;受累：0.24±0.10; p = 0.032），但在视乳头周围巩膜中无统计学显著差异（载体：0.46±0.15;受累：0.45±0.17; p = 0.68）。在受影响的狗中，中后巩膜（携带者：28.1±9.14;受影响的：18.3±5.12; p<0.0001）和视乳头周围巩膜（携带者：34.6±9.34;受影响的：21.1±6.97; p = 0.0002）的胶原密度在统计学上显著降低。结论ADAMTS 10基因突变犬在临床青光眼发病前存在明显的后巩膜胶原微结构改变。纤维胶原密度的减少可能是先前报道的该模型中巩膜机械弱化的重要促成因素。基线巩膜异常有可能与眼内压（IOP）升高相互作用，以确定疾病动物模型中青光眼进展的过程，并可能在人类青光眼中。
Purpose We aimed to characterize alterations in the posterior scleral collagen microstructure before detectable disease onset in a canine model of open-angle glaucoma caused by an ADAMTS10 mutation. Methods Collagen orientation, anisotropy degree (proportion of preferentially aligned collagen), and relative density were measured at 0.4 mm spatial resolution using synchrotron wide-angle X-ray scattering. For statistical evaluation of structure parameters, regional averages of the peripapillary and mid-posterior sclera were compared between ADAMTS10 mutant (affected) dogs (n = 3) and age-matched (carrier) controls (n = 3). Results No marked differences in the general pattern of preferential collagen fibril orientation were noted between the control and affected dogs. The peripapillary sclera of all specimens featured strongly aligned circumferential collagen ringing the optic nerve head. Collagen anisotropy was significantly reduced in the mid-posterior sclera of the affected dogs (carrier: 0.27±0.11; affected: 0.24±0.10; p = 0.032) but was not statistically significantly different in the peripapillary sclera (carrier: 0.46±0.15; affected: 0.45±0.17; p = 0.68). Collagen density was statistically significantly reduced in the affected dogs for the mid-posterior sclera (carrier: 28.1±9.14; affected: 18.3±5.12; p<0.0001) and the peripapillary sclera (carrier: 34.6±9.34; affected: 21.1±6.97; p = 0.0002). Conclusions Significant alterations in the posterior scleral collagen microstructure are present before the onset of clinical glaucoma in ADAMTS10 mutant dogs. A reduction in fibrous collagen density is likely an important contributory factor in the previously reported mechanical weakening of the sclera in this model. Baseline scleral abnormalities have the potential to interact with intraocular pressure (IOP) elevations in determining the course of glaucoma progression in animal models of the disease, and potentially in human glaucoma.