Wojcik Katarzyna A, Blasiak Janusz, Szaflik Jerzy, Szaflik Jacek P
Faculty of Biology and Environmental Sciences, Department of Molecular Genetics, University of Lodz, Łódź, Poland.
Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Kliniczny Szpital Okulistyczny, Warszawa, Poland.
Acta Biochim Pol. 2014;61(1):55-62. Epub 2014 Mar 18.
Keratoconus (KC) is a corneal disease associated with structural abnormalities in the corneal epithelium, Bowman's layer and stroma and altered concentration of tear components. KC corneas show a different pattern of collagen lamellae than their normal counterparts. Also, a reduction of several collagen types in KC epithelium and stroma was observed. Altered expression and/or activity of lysyl oxidase, a critical enzyme of the biogenesis of connective tissue detected in KC corneas, may weaken covalent bonds between collagen and elastin fibrils, what may lead to biomechanical deterioration of the cornea. Increased activity of matrix metalloproteinases observed in KC may induce the degradation of the extracellular matrix causing damage to the cornea. Oxidative and nitrative stress play an important role in KC pathogenesis and KC corneas are characterized by the disturbed lipid peroxidation and nitric oxide pathways. Malfunctioning of these pathways may lead to accumulation of their toxic by-products inducing several detrimental effects, along with apoptosis of the corneal cells, which may result from the loss of β-actin or increased levels of cytokines, including interleukin-1 and -6. Change in the expression of genes associated with wound healing, including the nerve growth factor and the visual system homeobox 1, may contribute to increased susceptibility of KC corneas to injury. Consequently, biochemical changes may play an important role in KC pathophysiology and, therefore, can be considered in prevention, diagnosis, prognosis and in the therapy of this disease as well.
圆锥角膜（KC）是一种与角膜上皮、Bowman层和基质的结构异常以及泪液成分浓度改变相关的角膜疾病。圆锥角膜的角膜显示出与正常角膜不同的胶原板层模式。此外，在圆锥角膜的上皮和基质中观察到几种胶原类型的减少。在圆锥角膜中检测到的赖氨酰氧化酶（一种结缔组织生物合成的关键酶）的表达和/或活性改变，可能会削弱胶原和弹性纤维之间的共价键，这可能导致角膜的生物力学恶化。在圆锥角膜中观察到的基质金属蛋白酶活性增加，可能会诱导细胞外基质的降解，从而对角膜造成损伤。氧化应激和硝化应激在圆锥角膜的发病机制中起重要作用，圆锥角膜的特征是脂质过氧化和一氧化氮途径紊乱。这些途径的功能失调可能导致其有毒副产物的积累，引发多种有害影响，包括角膜细胞的凋亡，这可能是由于β-肌动蛋白的丧失或细胞因子（包括白细胞介素-1和-6）水平的升高所致。与伤口愈合相关的基因表达变化，包括神经生长因子和视觉系统同源框1，可能导致圆锥角膜对损伤的易感性增加。因此，生化变化可能在圆锥角膜的病理生理学中起重要作用，因此在该疾病的预防、诊断、预后和治疗中也应予以考虑。
