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.

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-affected Corneas

“…Our study confirms the potential role of oxidative stress in KC-affected corneas. This is consistent with previous studies, suggesting the involvement of cellular stress in KC pathology 39,40 . We have identified differential expression of many genes involved in response to oxidative stress including GSTO1, SGK1, APOD, KLF9, GPX3, STK39, TXNIP, and lnc-ALDH3A2-2:1.…”

Cytokine Expression in Keratoconus and its Corneal Microenvironment: A Systematic Review

“…Elevated levels of IL-17 may induce tissue damage in KC and could relate to disease severity. 69 Indeed, the levels of IL-17A were shown to be associated with center Keratoconus-Index and Index-of-Surface Variance after CXL. 56 Although IL-17 is the principle cytokine produced by T helper17 (Th17) cells (Th17 cells are upregulated by TGF-ß and IL-6, which are themselves both upregulated in keratoconus cornea [31][32][33]70,71 ), it can be produced by many other cell types.…”

Pediatric keratoconus: a review of the literature

“…Additionally, lower levels of cystatin, inhibitors of cysteine proteases, have been found in the tears of patients with keratoconus, suggesting lower protein content in keratoconic eyes [26, 27]. It is the inadequate balance between pro- and anti-inflammatory cytokines that lead to altered corneal structure and function triggering metalloproteinases and keratocyte apoptosis [28–30]. …”