Nitrosative Stress, Mitochondrial Peptides, and Ferroptosis Markers in Corneal Epithelial Cells from Keratoconus Patients.
Demirkiran. Cahit C; Mete. Alper A; Demiryürek. Abdullah Tuncay AT; Saracaloglu. Ahmet A; Demiryürek. Şeniz Ş
Key Findings
- Humanin levels rose in stage 3 keratoconus patients
- Mitochondrial ORF peptide levels dropped across all stages
- Nitrosative stress markers (nitric oxide, 3‑nitrotyrosine) and ferroptosis markers were elevated in keratoconus tissue
Practical Outcomes
- For biohackers, the findings mainly highlight a possible link between mitochondrial peptides and eye disease, but they don’t provide actionable steps for longevity or performance. No dosage, supplement, or protocol recommendations are offered, so the study has limited direct use for everyday health optimization.
Summary
The study found that in people with the eye condition keratoconus, a mitochondrial peptide called humanin was higher in more severe cases, while another mitochondrial peptide was lower, and signs of nitrosative stress and a type of cell death called ferroptosis were increased. This suggests these peptides and stress pathways might play a role in the disease, but the research does not test any treatments or give dosing advice.
Abstract
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. 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. Humanin levels in keratoconus corneal epithelial cells were increased in stage 3 (<i>p</i> < .05), while mitochondrial open-reading frame of the 12S rRNA-c (<i>p</i> < .01) levels were diminished in all stages. Significant increases in nitric oxide (<i>p</i> < .001) and 3-nitrotyrosine (<i>p</i> < .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 (<i>p</i> < .01), while long-chain fatty acid CoA ligase 4 (<i>p</i> < .05) and malondialdehyde (<i>p</i> < .05) levels were increased. 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.
Study Information
pubmed
2025
2025-10-14T00:00:00.000Z
10.1080/02713683.2025.2570815
38