April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Role of proteasomal proteolysis in the pathogenesis of macular corneal dystrophy
Author Affiliations & Notes
  • Eszter Szalai
    Department of Ophthalmology, University of Deberecen, Medical and Health Science Center, Debrecen, Hungary
  • Kai Kaarniranta
    Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Laszlo Modis Jr.
    Department of Ophthalmology, University of Deberecen, Medical and Health Science Center, Debrecen, Hungary
  • Andras Berta
    Department of Ophthalmology, University of Deberecen, Medical and Health Science Center, Debrecen, Hungary
  • Adrian Smedowski
    Ophthalmology Clinic, District Railway Hospital, Katowice, Poland
  • Johanna Viiri
    Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
  • Bogumil Wowra
    Ophthalmology Clinic, District Railway Hospital, Katowice, Poland
  • Dariusz Dobrowolski
    Ophthalmology Clinic, District Railway Hospital, Katowice, Poland
  • Edward Wylegala
    Ophthalmology Clinic, District Railway Hospital, Katowice, Poland
  • Szabolcs Felszeghy
    Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
  • Footnotes
    Commercial Relationships Eszter Szalai, None; Kai Kaarniranta, None; Laszlo Modis Jr., None; Andras Berta, None; Adrian Smedowski, None; Johanna Viiri, None; Bogumil Wowra, None; Dariusz Dobrowolski, None; Edward Wylegala, None; Szabolcs Felszeghy, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1018. doi:
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      Eszter Szalai, Kai Kaarniranta, Laszlo Modis Jr., Andras Berta, Adrian Smedowski, Johanna Viiri, Bogumil Wowra, Dariusz Dobrowolski, Edward Wylegala, Szabolcs Felszeghy; Role of proteasomal proteolysis in the pathogenesis of macular corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1018.

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

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Abstract

Purpose: Macular corneal dystrophy (MIM #217800), an autosomal recessive disorder primarily affecting the corneal stroma, is characterized by abnormal accumulation of glycosaminoglycans. Our goal was to analyse the expression level of protein aggregation regulatory molecules in human macular dystrophy corneas and in cultured human corneal epithelial cells (HCE-2) under proteasomal inhibition in vitro.

Methods: Four cases of macular dystrophy and 4 normal human corneal buttons collected during corneal transplantation were examined for their expression patterns of Heat shock protein 70 (Hsp70), SQSTM1/p62 and ubiquitin protein conjugates by fluorescent immunohistochemistry. Expression levels in response to different concentrations of proteasomal inhibitor treatment (MG-132) were also analysed in HCE-2 cells by western blotting and transmission electron microscopy.

Results: In macular dystrophy samples, strongly upregulated Hsp70, SQSTM1/p62 and ubiquitin protein conjugates were observed in basal epithelial cells. Weak Hsp70 labelling, moderate ubiquitin and SQSTM1/p62 positivity were present in stromal keratocytes in macular dystrophy. All the studied proteins were also highly elevated under proteasomal inhibition in HCE-2 cells in vitro.

Conclusions: This study first demonstrates the upregulation of Hsp70, SQSTM1/p62 and ubiquitin protein conjugates in the basal epithelial cells and stromal keratocytes in macular dystrophy. Our data may support the role of impaired ubiquitin/proteasomal protein degradation and abnormal protein homeostasis in the pathogenesis of macular corneal dystrophy.

Keywords: 480 cornea: basic science • 596 microscopy: confocal/tunneling • 597 microscopy: electron microscopy  
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