July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The genetic basis of Fuchs endothelial corneal dystrophy and stem cell regeneration of corneal endothelium
Author Affiliations & Notes
  • Natalie A. Afshari
    Ophthalmology, University of California, San Diego, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Natalie Afshari, None
  • Footnotes
    Support  R01 EY023196, R01 EY016482, R01 EY016514, R01 EY016835, R21 EY015145 and P30 EY11373
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3914. doi:
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    • Get Citation

      Natalie A. Afshari; The genetic basis of Fuchs endothelial corneal dystrophy and stem cell regeneration of corneal endothelium. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3914.

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

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Presentation Description : A genome-wide association study (GWAS) on 1,404 patients with Fuchs endothelial corneal dystrophy (FECD) and 2,564 controls was performed. This GWAS was followed by replication and meta-analysis for a total of 2,075 cases and 3,342 controls.

We identified three significant novel loci (P<5 x 10^-8): KANK4 rs79742895, LAMC1 rs3768617 and ATP1B1 rs1200114. We also found a strong signal from the established TCF4 locus.

Each of those genes have a possible role in the pathogenesis of FECD: KANK4 and LAMC1 may be involved in maintaining the endothelial cell layer, while ATP1B1 likely functions in fluid transport. These findings may shed light on the biochemical pathogenesis of FECD.

Furthermore, we have developed a novel small molecule-based approach to derive human corneal endothelial cells from stem cells (PSCs) via ocular lineage specification. For regeneration of cornel endothelium, the fate of stem cells was restricted to the eye field-like state and the cells became eye field stem cells (EFSCs). In the second phase, PSC-derived EFSCs were further directed toward either neural crest lineage or retinal lineage. The corneal endothelial cells were directly induced from ocular neural crest stem cells (NCSCs) by suppressing TGF-β and ROCK signaling. EFSC derived NCSCs could serve as an immediate source cell for rapid corneal endothelial cell induction.

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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