Nrf2- and PGC-1 α -deficient mice: A novel animal model for impaired autophagy in AMD?
2015; Wiley; Volume: 93; Linguagem: Inglês
10.1111/j.1755-3768.2015.0541
ISSN1755-3768
AutoresJussi J. Paterno, Adrian Smędowski, Maria Hytti, Geir Bjørkøy, Marialaura Amadio, Anna‐Liisa Levonen, Pasi Tavi, Anu Kauppinen, Kai Kaarniranta,
Tópico(s)Retinoids in leukemia and cellular processes
ResumoPurpose To clarify the complex role of impaired autophagy in RPE damage, we analysed mice deficient in both Nrf2 and PGC-1α. Increasing evidence of impaired autophagy as a contributor to AMD has raised the importance of animal models that fundamentally mimic autophagy decline in RPE. Methods We analysed morphological and immunohistochemical changes in the retina of aged Nrf2 and PGC-1α double knock-out (dKO) mice and wild-type controls. The Keap1-Nrf2 pathway, an essential system involved in oxidative stress response, is regulated by proteasomes and autophagy. PGC-1α is a master regulator of ROS-scavenging enzymes, and it has a role in inducing autophagy/mitophagy. We performed immunostaining of proteins related to oxidative stress and autophagy (4-HNE, Beclin-1, HuR, LC3, p62, and ubiquitin). Results RPE degeneration was prominent in dKO mice and it was associated with changes in autophagy and oxidative stress. Conclusions Our findings suggest Nrf2 and PGC-1α deficiency increases oxidative stress and affects autophagy. This coincides with the retinal degeneration observed in the promising new AMD mouse model.
Referência(s)