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Ex vivo 3D human corneal stroma model for Schnyder corneal dystrophy - role of autophagy in its pathogenesis and resolution

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dc.contributor.authorSzabó, Dóra Júlia
dc.contributor.authorNagymihály, Richárd
dc.contributor.authorVeréb, Zoltán
dc.contributor.authorJosifovska, Natasha
dc.contributor.authorNoer, Agate
dc.contributor.authorLiskova, Petra
dc.contributor.authorFacskó, Andrea
dc.contributor.authorMoe, Morten C.
dc.contributor.authorPetrovski, Goran
dc.date.accessioned2022-04-07T08:25:56Z
dc.date.available2022-04-07T08:25:56Z
dc.date.issued2018
dc.description.abstractIntroduction. Multilamellar bodies (MLBs) are concentric cytoplasmic membranes which form through an autophagy-dependent mechanism. In the cornea, the 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 stromaderived 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, 10 mM) for 24 hours. Results. CSMSCs can form spontaneously 3D outgrowths over a 3-4 weeks period, depositing their 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 a 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.es
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dc.identifier.citationHistology and Histopathology, Vol.33, nº5, (2018)
dc.identifier.doiDOI: 10.14670/HH-11-928
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/118846
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCorneal stroma-derived mesenchymal stemlike cells (CSMSC)es
dc.subjectSchnyder corneal dystrophyes
dc.subject3D modeles
dc.subjectAutophagyes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleEx vivo 3D human corneal stroma model for Schnyder corneal dystrophy - role of autophagy in its pathogenesis and resolutiones
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.33, nº5 (2018)