July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Transcriptomic analysis of corneas from Keratoconus patients in Saudi Arabia and the United States.
Author Affiliations & Notes
  • Nan Hu
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Vishal Shinde
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • James W Foster
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Uri Soiberman
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Yassine Jamil Daoud
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Alka Mahale
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Samar A Al-Swailem
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Albert Jun
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Shukti Chakravarti
    Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Nan Hu, None; Vishal Shinde, None; James Foster, None; Uri Soiberman, None; Yassine Daoud, None; Alka Mahale, None; Samar Al-Swailem, None; Albert Jun, None; Shukti Chakravarti, None
  • Footnotes
    Support  NIH.NEI RO1EY026104, KKESH Saudi Arabia and Wilmer Eye Institute funds
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2922. doi:
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      Nan Hu, Vishal Shinde, James W Foster, Uri Soiberman, Yassine Jamil Daoud, Alka Mahale, Samar A Al-Swailem, Albert Jun, Shukti Chakravarti; Transcriptomic analysis of corneas from Keratoconus patients in Saudi Arabia and the United States.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2922.

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

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Abstract

Purpose : Keratoconus (KC) involves progressive thinning of the cornea, loss of vision and in severe cases cornea transplantation. There is a higher incidence of keratoconus in Saudi Arabia, often taking a more severe form. To elucidate underlying disease mechanisms we performed comparative transcriptomic analyses of corneas from keratoconus patients in Saudi Arabia and the United States.

Methods : Corneas were obtained from keratoconus patients undergoing cornea transplantation in Saudi Arabia and the Wilmer Eye Institute in Baltimore. Donor (DN) corneas were obtained from Lions Eye Bank, Baltimore and the Lions Eye Institute for transplant and research, Florida. Total RNA was isolated using TRizol (Thermo Fischer Scientific) and samples with RNA integrity (2100 Bioanalyzer) number more than or equal to 7 were sequenced using Illumina HiSeq2500 (Macrogen, USA) at 50 million paired reads. Genome Alignment was performed using STAR software. Functional annotations were performed using PANTHER gene ontology tools.

Results : The KC samples from Baltimore were either stroma only, or stroma and epithelial (epi) layers, while the Saudi Arabia samples were largely epithelial and stroma, with a few full thickness corneas (Ft). A total number of transcripts detected ranged from 22,507 to33,155 in the Baltimore cohort and 25,787 to 36,946 in Saudi Arabia cohort. The principal component analysis shows separation of 8/12 Saudi Arabian and 3/8 Baltimore KC from the donor samples. The Saudi Arabian and Baltimore samples were also separated from one another. The KC samples grouped into the stroma, epi and stroma, and Ft, compared to donor samples identified 165 transcripts that were commonly changed in all KC groups. Increased transcripts (11/165) include galactosyltransferase, B3GALT5, ADAMTS14, a metalloproteinase, that cleaves procollagen I before it can form fibrils, and carbonic anhydrase CA6. Decreases included genes that regulate metabolism (ADH1B, CA3, CA6) transcription (ATF3, MAFF, KLF6) and cell growth and death (GADD45A and 45B, CDC42EP2).

Conclusions : The common changes primarily decreased in transcripts that regulate cell survival, growth, and apoptosis. Thus, the well-documented connective tissue decreases in keratoconus may ultimately correlate with deeper cellular dysfunctions.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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