Changes in corneal mechanics due to glycosaminoglycan depletion and corneal cross-linking therapy

项目摘要 未经矫正的屈光不正是全世界视力受损的最常见原因。这个 角膜和晶状体是眼睛的主要屈光元素，它们协同工作，将入射的光线聚焦在 视网膜；当角膜或晶状体不能正常工作时，就会发生屈光不正。据估计， 屈光不正影响了大约1.5亿美国人，他们每年在眼镜上的支出超过150亿美元。 根据国民健康与营养调查结果，超过1.1亿人 美国人可以通过屈光矫正获得正常视力。术后可能发生角膜扩张症 屈光手术，如LASIK和PRK。除了LASIK术后的角膜扩张外， 每2000名美国人中就有一人患有进行性圆锥角膜，目前仍是角膜病变的指征。 移植。这种疾病的进行性显著影响患者的心理健康和生活质量。 病人。换句话说，圆锥角膜对公众健康的影响与其相对较低的比例是不成比例的。 流行，因为它主要影响非常年轻的成年人。角膜交联术(CXL)是一种 相对安全有效的方法来减缓或完全阻止圆锥角膜的进展。它有 也被用来稳定甚至提高容易发生术后扩张的患者的视力 LASIK手术。然而，即使经过多年的研究，这种治疗的确切机制 程序还没有完全理解。圆锥角膜与胶原纤维的破坏有关， 蛋白多糖含量降低，角膜生物力学强度显著降低。一目了然 了解赋予角膜细胞外基质弹性的机制提供了 为改进标准CXL程序甚至开发新的CXL程序提供必要的信息 疾病状态下的治疗干预。在这项R21级别的研究中，国际和平研究所建议 探讨CXL治疗与角膜细胞外基质超微结构的关系。这 该项目描述了胶原纤维、糖胺聚糖和胶原纤维的结构作用。 糖胺多聚糖相互作用。为此，角膜样本的机械反应的变化 随后将测量糖胺多糖的降解和角膜的交联度。建议数 研究具有创新性，因为它将设计出一个新颖而独特的框架，用于对 角膜交联术的硬化效应。在完成这项R21研究并量化之后 胶原原纤维微结构和糖胺多糖组成的可能结构作用 CXL治疗的有效性，我们将寻求R01水平的资金，以扩大我们的研究 计划并进一步研究角膜组织在损伤和疾病中的生物力学。

Project Summary The uncorrected refractive error is the most common cause of impaired vision throughout the world. The cornea and the lens, the main refractive elements of the eye, work in tandem to focus the incoming light on the retina; refractive errors occur when either the cornea or the lens fails to function properly. It is estimated that refractive errors affect about 150 million Americans who spend over $15 billion each year on eyewear. According to National Health and Nutrition Examination Survey results, over one hundred and ten million Americans could achieve normal vision with refractive correction. Corneal ectasia may happen after refractive surgical procedures such as LASIK and PRK. In addition to corneal ectasia after LASIK, progressive keratoconus affects one in every 2000 Americans and is still an indication for corneal transplant. The progressive nature of this disease significantly affects the mental health and quality of life of patients. In other words, the public health impact of keratoconus is disproportionate to its relatively low prevalence because it primarily affects very young adults. Corneal cross-linking (CXL) treatment is a relatively safe and efficient method to slow down or completely arrest the progression of keratoconus. It has also been used to stabilize and even improve the visual acuity in patients prone to develop ectasia after LASIK. Nevertheless, even after years of research, precise mechanisms underlying this treatment procedure are not fully understood. Keratoconus is associated with the disruption of the collagen fibrils, decreased proteoglycan content, and a significant reduction in corneal biomechanical strength. A clear understanding of the mechanisms that confer elasticity to corneal extracellular matrix provides the necessary information for improvement of the standard CXL procedure and even development of new therapeutic intervention in the diseased states. In this R21-level research study, the PI proposes to investigate the interrelation between CXL therapy and ultrastructure of corneal extracellular matrix. This project characterizes the structural roles of the collagen fibrils, glycosaminoglycans, and collagen fibril– glycosaminoglycan interactions. To this end, the changes in mechanical response of corneal samples following glycosaminoglycan degradation and corneal cross-linking will be measured. The proposed research is innovative because it will devise a novel and unique framework for rigorous investigation of the stiffening effects of the corneal cross-linking therapy. After completing this R21 study and quantifying possible structural roles of collagen fibrils microstructure and glycosaminoglycan composition in effectiveness of the CXL treatment, we will pursue R01 level funding in order to extend our research program and further investigate the biomechanics of corneal tissue in injury and disease.