Investigation of Mitophagy Biomarkers in Corneal Epithelium of Keratoconus Patients.

Erdost Yıldız, Dilara Aydemir, Noushin Zibandeh, Eda Kuşan, Koray Gümüş, Özge İlhan Saraç, Melisa Zişan Karslıoğlu, Nurullah Çağıl, Afsun Şahin

Current eye research 2022 May

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The pathological mechanisms of keratoconus (KC) have not been elucidated yet. Mitophagy is an important mechanism that eliminates damaged mitochondria under oxidative stress, and it could be one of the leading pathological causes of KC. This study aimed to find out the role of mitophagy in the keratoconic corneal epithelium. The corneal epithelia were collected from the 103 progressive KC patients and the 46 control subjects. The real-time quantitative PCR was performed for PTEN-putative kinase-1 (PINK1), PARKIN, p62, and BNIP3 gene expressions in 31 KC and 9 control subjects. Western blot analyses were performed to investigate the protein expressions of PINK1, PARKIN, LC3B, ATG5, and BECLIN in the remaining 109 corneal epithelium samples from 72 patients and 37 control subjects. mRNA and protein expressions of PINK1 decreased significantly in the corneal epithelium of KC patients compared to the control subjects. No significant change was found in mRNA levels of PARKIN, p62, and BNIP3 in KC patients. The protein expression of PARKIN, LC3B, ATG5, and Beclin did not significantly differ between KC patients and control subjects. Gene expression levels of mitophagy biomarkers were not affected by the KC grade. PINK1/PARKIN-dependent mitophagy is affected in the keratoconic corneal epithelium. We found significant decreases in both mRNA and protein expressions of PINK1 in the keratoconic corneal epithelium. However, we did not observe any other significant change in mitophagy markers. Mitochondrial stress-related mitophagy pathways could be interrupted by the decreased levels of PINK1 in the keratoconic corneal epithelium, but solely PINK1 dysregulation is not likely to induce KC pathogenesis.

Citation

Erdost Yıldız, Dilara Aydemir, Noushin Zibandeh, Eda Kuşan, Koray Gümüş, Özge İlhan Saraç, Melisa Zişan Karslıoğlu, Nurullah Çağıl, Afsun Şahin. Investigation of Mitophagy Biomarkers in Corneal Epithelium of Keratoconus Patients. Current eye research. 2022 May;47(5):661-669