Nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) regulates proteolysis in cornea

• Published in: Acta ophthalmologica (Oxford, England) Vol. 93; no. S255
• Main Authors: Smedowski, A., Paterno, J.J., Amadio, M., Levonen, A.L., Tavi, P., Kaarniranta, K., Wylegala, E.
• Format: Journal Article
• Language: English
• Published: 01.10.2015
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2015.0486

Purpose The cornea is exposed to constant oxidative stress that may lead to protein homeostasis imbalance and tissue damage during aging process. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems to clean damaged proteins in cells. Our aim was to investigate the role of the Nrf2 and PGC‐1α, the central transcription factors of the regulation of cellular detoxification and defense against oxidative stress, in corneas of double knockout mice (Nrf2‐/PGC1α‐). Methods After fixation in 4% PFA, eyeballs were embedded in paraffin and 5 μm cross sections were cut using microtome. Tissue sections were deparaffinized, rehydrated and processed for immunostaining with primary antibodies against Beclin, HuR, p62 and LC3. Results were compared with age matching wild type controls. Results Deficiency of Nrf2 and PGC‐1α evoked accumulation of proteasomal ubiquitin and autophagy markers p62, Beclin and LC3 in one year old animals. Moreover, HuR that regulates p62 expression was highly up‐regulated in the cornea epithelium. Conclusions These results suggest that Nrf2 and PGC‐1α deficiency associates with the impaired proteasomal and autophagy clearance in the corneal epithelium. This might be linked to corneal diseases, such as macular dystrophy (Kaarniranta et al., 2015).