Computational approaches for identifications of altered ion channels in keratoconus.

Background: Keratoconus is an etiologically complex, degenerative corneal disease that eventually leads to loss of corneal integrity. Cells in corneal epithelium and endothelium express various types of ion channels that play important roles in ocular pathology. This emphasizes the need of understanding alterations of ion channels in keratoconus.

Method: Differential gene expression analysis was performed to identify deregulated ion channels in keratoconus patients using transcriptomic data. Thereafter correlation analysis of ion channel expression was performed to obtain the changed correlation between ion channels' expression in keratoconus patients versus control samples. Moreover, Protein-protein interaction networks and a pathway map was constructed to identify cellular processes altered due to the deregulation of ion channels. Furthermore, drugs interacting with deregulated ion channels were identified.

Results: Total 75 ion channels were found to be deregulated in keratoconus, of which 12 were upregulated and 63 were downregulated. Correlations between ion channel expressions found to be different in control and keratoconus samples. Thereafter, protein-protein interactions network was generated to identify hub ion channels in network. Furthermore, the pathway map was constructed to depict calcium signalling, MAPK signalling, synthesis and secretion of cortisol, and cAMP signalling. The 19 FDA- approved drugs that interact with the 5 deregulated ion channels were identified.

Conclusion: Down-regulation of voltage-gated calcium channels can be attributed to reduced cell proliferation and differentiation. Additionally, deregulated ion channels in 3',5'- cyclic adenosine monophosphate signalling may be responsible for elevated cortisol level in progressive keratoconus patients.