June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Two Novel microRNA Mutations Related with Keratoconus
Author Affiliations & Notes
  • Nurullah Cagil
    Department of Ophtalmology, Yildirim Beyazit University, Ankara, Turkey
  • Serhat Sevli
    Nehir Biyoteknoloji, Ankara, Turkey
  • Nagihan Ugurlu
    Department of Ophtalmology, Yildirim Beyazit University, Ankara, Turkey
  • Ozge Ilhan Sarac
    Department of Ophtalmology, Yildirim Beyazit University, Ankara, Turkey
  • Footnotes
    Commercial Relationships Nurullah Cagil, None; Serhat Sevli, Nehir Biyoteknoloji (E); Nagihan Ugurlu, None; Ozge Ilhan Sarac, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2997. doi:
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      Nurullah Cagil, Serhat Sevli, Nagihan Ugurlu, Ozge Ilhan Sarac; Two Novel microRNA Mutations Related with Keratoconus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2997.

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

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Purpose: Keratoconus (KC) is a complex disease of which pathogenesis results due to multiple environmental and genetic factors. Although suspected environmental effects, some chromosomal regions are thought to have role in KC. We sequenced 6 microRNAs located on KC related genomic regions to check the hypothesis of there would be nucleotide variations for molecular diagnosis of KC.

Methods: Data mining of previous literature gave us the chromosomal regions which may contain genetic variations related with KC. Additionally we analyzed the KC related stromal gene expression research articles and listed the proteins that are overexpressed in corneal epithelial and stromal tissue of KC patients. We listed the microRNAs located on those genomic regions and searched for their target mRNAs in silico. By matching the two lists, we obtained 5 miRNAs (miR143, miR145, miR198, miR29b1, miR1224) that have potential to target genes which are overexpressed in KC cornea. Later, we added miR184 in our sequencing list since this microRNA was previously shown to have a novel mutation in KC patient. All the sequencing research were performed by Sanger method and 86 peripheric blood samples were analyzed in total.

Results: We obtained 2 important mutations inside miR145 and miR29b1 gene sequences in two different KC patients. These mutation are not observed in healty first degree relatives of them. Both two patients are heterozygote for those 2 mutations. Additionally, 11 of the patients have a novel mutation at the forward sequence of their miR29b1 gene, however, one of the patients healty relative also possess this variation and two of the patients’ relatives having KC do not have the indicated mutation.

Conclusions: In silico analysis shown that miR145 possibly targets MMP13 and PAI1 that are overexpressed in cornea with KC. Similarly, miR29b1 SP1 and COL1A1 that are also overexpressed in cornea with KC. SP1 is a transcription factor and regulates the expression ratio of PAI1, CCND2, LOX, MUC4, AND KRT5 (all of them are shown to be overexpressed in KC stroma of epithelial tissue.) Thus their overexpression may be related with mutations in miR145 and miR29b1. Of course, further research will be performed for determination of the frequency of mutations in a larger population, for relating detected mutation with overexpressed genes in a cell culture model.


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