June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The Nrf2 and PGC-1α deficient murine retina reveals retinal pigment epithelium damage that coincides with autophagy decline and damaged mitochondria.
Author Affiliations & Notes
  • Jussi J Paterno
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Niko Kivinen
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Johanna Viiri
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Juha Hyttinen
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Ali Koskela
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Mateusz Winiarczyk
    Department of Vitreoretinal Surgery, Medical University of Lublin, Lublin, Poland
  • Deborah A Ferrington
    Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States
  • Szabolcs Felszeghy
    Institute of Biomedicine and Institute of Dentistry, University of Eastern Finland, Kuopio, Finland
  • Anu Kauppinen
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
  • Kai Kaarniranta
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Footnotes
    Commercial Relationships   Jussi Paterno, None; Niko Kivinen, None; Johanna Viiri, None; Juha Hyttinen, None; Ali Koskela, None; Mateusz Winiarczyk, None; Deborah Ferrington, None; Szabolcs Felszeghy, None; Anu Kauppinen, None; Kai Kaarniranta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5363. doi:
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      Jussi J Paterno, Niko Kivinen, Johanna Viiri, Juha Hyttinen, Ali Koskela, Mateusz Winiarczyk, Deborah A Ferrington, Szabolcs Felszeghy, Anu Kauppinen, Kai Kaarniranta; The Nrf2 and PGC-1α deficient murine retina reveals retinal pigment epithelium damage that coincides with autophagy decline and damaged mitochondria.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5363.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Increased oxidative stress has been linked to the degeneration of retinal pigment epithelial cells (RPE) during aging process. Nuclear factor-erythroid 2-related factor-2 (Nrf2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are transcription factors that regulates reactive oxygen species (ROS) balance. We generated Nrf2–/– PGC-1α–/– double knock-out (DKO) mouse model to study morphological alterations and autophagy markers in RPE.

Methods : Retinal tissue sections of DKO mice and age-matched wild-type controls on a C57BL/6J background, sacrificed at one years of age, were processed for transmission electron microscopy (TEM) and immunohistolochemical microscopy analysis. Immunohistochemical stainings were done for oxidative stress marker 4-HNE and autophagy regulators p62/SQSTM1, Beclin-1, LC3 and ubiquitin protein conjugates. Eye fundus imaging was performed to assess retina in vivo.

Results : In the RPE of DKO mice, number of autophagosomes were increased (p<0.01), together with upregulation of p62/SQSTM1, Beclin-1, LC3 and ubiquitin protein conjugates. DKO mice model showed clearly increased number of damaged mitochondria (p<0.001), while number of melanosomes were decreased (p<0.05). No signs of retinal or choroidal neovascularization were seen in vivo.

Conclusions : Our findings support that dissecting the ROS regulating pathways in the RPE of the Nrf2 and PGC-1α deficient mice is associated with autophagy decline and mitochondrial dysfunction. As these are important features in the ageing eye and degeneration of RPE cells, this animal model appears to have applications for experimental research of dry age-related macular degeneration and its treatment.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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