角膜力学行为及其与角膜疾病的关联

Cornea is an important refractive tissue, whose physiological and pathological mechanisms are closely related to its structure and biomechanical properties. For example, decreased corneal biomechanical properties can lead to keratoconus and progressive post-LASIK keratectasia(PPLK),which are the most important factor in producing corneal blindness. In our country，the incidence of corneal blindness ranked second in all the blinding eye diseases. Although pathogenesis of these diseases is still unclear now, crosslinking treatment in these diseases aimed at improving corneal biomechanical properties has brought initial success, which reveals the feasibility of treating these diseases by improving biomechanical properties. As a result, research in corneal biomechanical properties in macro and micro perspective can result in definite cornea pathological mechanism and reliable clinical treatment, which possesses great theoretical and practical significances. On the basis of our prestudy, systemic microscopic and macroscopic experiments will be conducted to observe corneal structure and biomechanical properties, and weakened - normal - enhanced corneal collagen fibers gradient spectrum will be set up to verify structure and biomechanical properties of corneal collagen fibers as well as multiscaled biomechanical characteristics of corneal macroscopic biomechanical behavior. We will also establish association model of corneal macro- and micro-biomechanical behavior, which will be linked with clinical research to reflect fully and truly the related corneal physiological and pathological features, thus reveal the fundamental role of corneal biomechanical properties in pathogenesis and treatment of keratoconus and PPLK.

角膜是重要的屈光组织，其生理和病理机制与其结构和力学特性紧密关联。例如，角膜力学性质减弱造成圆锥角膜、准分子激光原位角膜磨镶术后进行性角膜扩张（PPLK）等疾病，构成了角膜盲的最重要因素。尽管上述疾病的发病机理至今未能完全阐明，然而，在对此类疾病的治疗中，从力学角度出发进行角膜胶原纤维交联，改善角膜力学性能却获得了阶段性成功，揭示了从力学角度治疗此类疾病的可行性。因此，对角膜宏微观力学性能的深入研究，对阐明角膜病理、建立可靠的临床治疗方法具有重要理论和现实意义。本项目拟在前期研究基础上通过对角膜结构和力学性能进行系统的微宏观实验，建立角膜胶原纤维减弱-正常-增强力学性能渐变谱，探明角膜胶原纤维的结构、力学特性和角膜宏观力学行为的多尺度力学特征，建立角膜宏微观力学行为的关联模型，并结合临床，使模型真实地反映角膜生理和病理特征，揭示角膜力学因素在圆锥角膜和PPLK等疾病中致病和治疗的根本作用。

角膜是重要的屈光组织，其生理和病理机制与其结构和力学特性紧密关联。角膜力学性质减弱造成圆锥角膜、准分子激光原位角膜磨镶术后进行性角膜扩张（PPLK）等疾病，构成了角膜盲的重要因素之一。上述疾病的发病机理至今未能完全阐明，在对此类疾病的治疗中，从力学角度出发进行角膜胶原纤维交联，改善角膜力学性能已获得了阶段性成功，揭示了从力学角度治疗此类疾病的可行性。因此，对角膜宏微观力学性能的深入研究，对阐明角膜病理、建立可靠的临床治疗方法具有重要理论和现实意义。本项目通过对角膜结构和力学性能进行系统的微宏观实验，发现使用Ⅱ型胶原酶作用角膜后，角膜曲率增加，厚度减小，生物力学强度下降，可以作为一种可靠的在体角膜扩张动物模型。在已建立的角膜扩张模型的基础上，通过免疫组化等相关试验手段，检测到活性氧簇通路中Nrf2、HO-1、Nox2氧化应激相关蛋白的表达增强，推测在角膜扩张模型中存在Nrf2/HO-1抗氧化通路代偿性的激活。同时发现莱菔硫烷对圆锥角膜具有一定的保护作用。京尼平交联角膜后，角膜曲率减小，生物力学强度增强，交联效果与紫外线核黄素类似，而安全性优于紫外线核黄素交联。结合圆锥角膜患者、LASIK术后患者及正常人的角膜形态学及力学测量，进一步揭示角膜力学因素在圆锥角膜和PPLK等疾病中致病和治疗的根本作用。