title: Role of biochemical factors in the pathogenesis of keratoconus.
abstract: 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.
authors.affiliation: Faculty of Biology and Environmental Sciences, Department of Molecular Genetics, University of Lodz, Łódź, Poland.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Wojcik
authors.affiliation: Faculty of Biology and Environmental Sciences, Department of Molecular Genetics, University of Lodz, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Kliniczny Szpital Okulistyczny, Warszawa, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Kliniczny Szpital Okulistyczny, Warszawa, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D000199:Actins / Q000378:metabolism; D050541:Bowman Membrane / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D019573:Epithelium, Corneal / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013666:Tears / Q000378:metabolism*
chemical_list: D000199:Actins; D003094:Collagen