Abstract:
Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA\'s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA\'s positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly.
摘要:
与蛋白聚糖交织的高度组织化的胶原纤维形成角膜的关键结构并促进其透明度。意外伤害造成的角膜疤痕,手术,或者感染改变了这个高度组织化的组织,造成严重后果,包括失明。没有有效和安全地治疗过度角膜瘢痕的药物或手术方法。因此,我们测试了合理设计的抗胶原抗体(ACA)的抗角膜瘢痕作用,该抗体的抗纤维化作用已在非眼模型中得到证实.利用带有切口角膜伤口的兔子模型,我们分析了ACA对瘢痕新生组织中富含胶原和蛋白聚糖的细胞外基质形成的影响。我们使用显微镜和光谱技术来量化这些成分,并测量表征胶原纤维结构和组织的关键参数。此外,我们分析了正常角膜和愈合角膜中胶原蛋白和蛋白聚糖的空间分布。我们的研究表明,在瘢痕新组织中合成的分析分子的质量和数量发生了显着变化。结果表明,这些变化超出了切口边缘。它还显示了ACA对定义适当角膜结构的一些关键参数的积极影响。这项初步研究为将来针对角膜细胞外瘢痕基质组装的治疗方法的测试提供了垫脚石。