June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Ex vivo 3D human corneal stroma model for Schnyder corneal dystrophy - role of autophagy in its pathogenesis and resolution
Author Affiliations & Notes
  • Dora Julia Szabo
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
  • Richárd Nagymihály
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
  • Zoltán Veréb
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
  • Natasha Josifovska
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
  • Agate Noer
    Center of Eye Research, Department of Ophthalmology, University of Oslo, Oslo, Norway
  • Petra Liskova
    Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Pragu, Czech Republic
  • Andrea Facskó
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
  • Morten Moe
    Center of Eye Research, Department of Ophthalmology, University of Oslo, Oslo, Norway
  • Goran Petrovski
    Department of Ophthalmology, University of Szeged, Szeged, Hungary
    Center of Eye Research, Department of Ophthalmology, University of Oslo, Oslo, Norway
  • Footnotes
    Commercial Relationships   Dora Szabo, None; Richárd Nagymihály, None; Zoltán Veréb, None; Natasha Josifovska, None; Agate Noer, None; Petra Liskova, None; Andrea Facskó, None; Morten Moe, None; Goran Petrovski, None
  • Footnotes
    Support  HARVO Travel Grant 2017
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1398. doi:
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      Dora Julia Szabo, Richárd Nagymihály, Zoltán Veréb, Natasha Josifovska, Agate Noer, Petra Liskova, Andrea Facskó, Morten Moe, Goran Petrovski; Ex vivo 3D human corneal stroma model for Schnyder corneal dystrophy - role of autophagy in its pathogenesis and resolution. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1398.

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

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Abstract

Purpose : Multilamellar bodies (MLBs) are concentric cytoplasmic membranes which form through an autophagy-dependent mechanism. In the cornea, presence of MLBs is associated with Schnyder corneal dystrophy (SCD). Ex vivo 3D modelling of the corneal stroma and SCD can help study pathogenesis and resolution of the disorder.

Methods : Corneal stroma explants were isolated from cadavers and cultivated long-term for more than 3 months to achieve spontaneous 3D outgrowth of corneal stroma-derived mesenchymal stem-like cells (CSMSCs). The 3D tissues were then examined by transmission electron microscopy (TEM) for presence of MLBs, and by immunofluorescent labelling against markers for autophagy (p62, LC3). Autophagy was induced by classical serum starvation or rapamycin (RAP) treatment (50nM), and inhibited by the autophagy inhibitor 3-methyladenine (3-MA, 10mM) for 24 hours.

Results : CSMSCs can form spontaneously 3D outgrowths over a 3-4 weeks period, depositing own extracellular matrix containing collagen I. TEM confirmed the presence of MLBs in the long-term (>3 months) 3D cultures, which became more abundant under starvation and RAP treatment, and decreased in number under autophagy inhibition with 3-MA. The presence of autophagy and its disappearance could be confirmed by an inversely related increase and decrease in the expression of LC3 and p62, respectively.

Conclusions : MLB formation in long-standing CSMSC cultures could serve as potential ex vivo model for studying corneal stroma diseases, including SCD. Inhibition of autophagy can decrease the formation of MLBs, which may lead to a novel treatment of the disease in the future.

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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