The triggering factors and etiology of KC is still poorly understood. A number of studies have reported the deregulation of genes, cytokines, enzymes, and other biomarkers in KC patients.
14,21 We have previously demonstrated elevation of MMP-9 and IL-6 expression in KC tears as well mRNA expression in corneal epithelium.
22 Conversely, we observed a severity-dependent reduction of Lysyl oxidase (LOX), Collagen IA1 (COL IA1), and Collagen IVA1 (COL IVA1) expression at both the mRNA and protein levels.
22,23 In KC, the changes in collagen content and enzymes involved in maintaining corneal structure are deregulated.
23,24 Matrix metalloproteinases are a set of enzymes that respond to injury or stress leading to remodeling of the extracellular matrix.
25 Matrix metalloproteinase-9 is secreted by the cornea
26 and has been implicated in KC
22,23 apart from other diseases. Matrix metalloproteinase-9 activity is upregulated by inflammatory cytokines TNF-α and IL-6,
22 which consequently causes degradation of type I and IV collagen in eye disease.
27 Therefore, factors affecting alteration in collagen structure of the KC cornea
24,28–30 could be targets to manage this disease, which currently does not have any medicines or eye drops for treatment. The copper-amine oxidase, LOX,
31,32 cross links collagen and elastin
33 into insoluble fibers via oxidation of adjacent peptidyl lysines (epsilon amino group) to reactive aldehydes. Reduction of LOX levels in KC has been reported.
34 Additionally, a linkage study of familial and case-control KC patients suggests that LOX gene containing genomic loci may be associated with KC
35 although pathogenic mutants were not found.
36 We observed LOX to be reduced in KC
23 epithelium in a severity-dependent manner at both the mRNA expression and enzymatic activity levels. Keratoconus is thus characterized by an altered corneal gene expression
21 profile resulting in biomechanical changes
24,28,30 affecting the normal corneal structure.
29 Bone morphogenetic proteins (BMP) are a family of signaling factors belonging to the TGF-β superfamily and play important roles in embryonic development, extracellular matrix synthesis, tissue repair, and homeostasis.
37 Among these, BMP-7 was identified as a major signaling molecule for the development of mammalian eye and kidney.
38 Bone morphogenetic proteins-7 is a potent regulator of TGF-β signaling
39 by counteracting the epithelial mesenchymal transition pathways, which is used in therapy for tissue remodeling in corneal opacity.
40 Therefore, it is important to understand its role in the tissue remodeling process in KC.