Please use this identifier to cite or link to this item: https://doi.org/10.14670/HH-11-588

Title: A novel proteotoxic stress associated mechanism for macular corneal dystrophy
Issue Date: 2015
Publisher: F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
Citation: Histology and histopathology, Vol. 30, nº 8 (2015)
ISSN: 1699-5848
Related subjects: CDU::5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología
Keywords: Heat shock proteins
Macular corneal dystrophy
Misfolding
Protein aggregation
Ubiquitin/ proteasome pathway
Abstract: Macular corneal dystrophy is a rare autosomal recessive eye disease affecting primarily the corneal stroma. Abnormal accumulation of proteoglycan aggregates has been observed intra- and extracellularly in the stromal layer. In addition to the stromal keratocytes and corneal lamellae, deposits are also present in the basal epithelial cells, endothelial cells and Descemet's membrane. Misfolding of proteins has a tendency to gather into aggregating deposits. We studied interaction of molecular chaperones and proteasomal clearance in macular dystrophy human samples and in human corneal HCE-2 epithelial cells. Seven cases of macular corneal dystrophy and four normal corneal buttons collected during corneal transplantation were examined for their expression patterns of heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62. In response to proteasome inhibition the same proteins were analyzed by western blotting. Slitlamp examination, in vivo confocal cornea microscopy and transmission electron microscopy were used for morphological analyses. Heat shock protein 70, ubiquitin protein conjugates and SQSTM1/p62 were upregulated in both the basal corneal epithelial cells and the stromal keratocytes in macular corneal dystrophy samples that coincided with an increased expression of the same molecules under proteasome inhibition in the HCE-2 cells in vitro. We propose a novel regulatory mechanism that connects the molecular chaperone and proteasomal clearance system in the pathogenesis of macular corneal dystrophy.
Primary author: Kaarniranta, Kai
Szalai, Eszter
Smedowski, Adrian
Hegy, Zoltán
Kivinen, Niko
Viiri, Johanna
Wowra, Bogumil
Dobrowolski, Dariusz
Módis Jr, László
Berta, András
Wylegala, Edgar
Felszeghy, Szabolcs
URI: http://hdl.handle.net/10201/96265
DOI: https://doi.org/10.14670/HH-11-588
Document type: info:eu-repo/semantics/article
Number of pages / Extensions: 10
Rights: info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 International
Appears in Collections:Vol.30, nº8 (2015)

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