Wills Eye Hospital, Philadelphia, PA 19107, USA.
Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, Room 501, 1015 Walnut Street, Philadelphia, PA 19107, USA.
Int J Mol Sci. 2023 Aug 30;24(17):13438. doi: 10.3390/ijms241713438.
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.
高度有序的胶原纤维与蛋白聚糖交织在一起，构成了角膜的关键结构，并使其保持透明。意外损伤、手术或感染导致的角膜瘢痕改变了这种高度有序的组织，造成严重后果，包括失明。目前尚无有效的药理学或手术方法来治疗过度的角膜瘢痕。因此，我们测试了一种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部模型中得到证实。我们利用兔角膜切口模型，分析了 ACA 对形成富含胶原和蛋白聚糖的细胞外基质的影响。我们使用显微镜和光谱技术来定量分析这些成分，并测量表征胶原纤维结构和组织的关键参数。此外，我们还分析了正常和愈合角膜中胶原和蛋白聚糖的空间分布。我们的研究表明，瘢痕新生组织中合成的分析分子的质量和数量发生了显著变化。结果表明，这些变化不仅局限于切口边缘，而且 ACA 对一些定义正常角膜结构的关键参数也有积极影响。这项初步研究为未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一个契机。
