Nitrosative Stress, Mitochondrial Peptides, and Ferroptosis Markers in Corneal Epithelial Cells from Keratoconus Patients.

Purpose: To investigate the possible contribution of nitrosative stress, mitochondrial peptide levels (humanin and mitochondrial open-reading frame of the 12S rRNA-c), and ferroptosis parameters in corneal epithelial cells obtained from patients with keratoconus.

Methods: This prospective study was conducted on corneal epithelial cell samples taken from 75 adult patients with keratoconus and 25 age-matched postmortem controls. The Amsler-Krumeich classification was used for staging the keratoconus. All parameters, except nitric oxide, were measured by ELISA, and nitric oxide levels were determined by the chemiluminescence method.

Results: Humanin levels in keratoconus corneal epithelial cells were increased in stage 3 (p < .05), while mitochondrial open-reading frame of the 12S rRNA-c (p < .01) levels were diminished in all stages. Significant increases in nitric oxide (p < .001) and 3-nitrotyrosine (p < .05) levels were detected in the keratoconus group, indicating the involvement of nitrosative stress. In stage 3, glutathione peroxidase 4 levels were shown to be decreased (p < .01), while long-chain fatty acid CoA ligase 4 (p < .05) and malondialdehyde (p < .05) levels were increased.

Conclusion: This is the first study to show that humanin and mitochondrial open-reading frame of the 12S rRNA-c can participate in the pathophysiology of keratoconus. In addition to the mitochondrial peptides, our data suggest that increased nitrosative stress and ferroptosis may contribute to the pathophysiology of keratoconus.