title: Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy.
abstract: Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.
authors.forename: Emily
authors.identifier: http://orcid.org/0000-0001-9646-5643
authors.initials: E
authors.lastname: Khuc
authors.affiliation: Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California, United States of America.|Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California, United States of America.
authors.forename: Russell
authors.identifier: http://orcid.org/0000-0002-0830-7029
authors.initials: R
authors.lastname: Bainer
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.
authors.forename: Marie
authors.identifier: http://orcid.org/0000-0003-2207-9664
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.
authors.forename: Selene M
authors.initials: SM
authors.lastname: Clay
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Daniel J
authors.identifier: http://orcid.org/0000-0001-8303-2603
authors.initials: DJ
authors.lastname: Weisenberger
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.
authors.forename: Jacquelyn
authors.identifier: http://orcid.org/0000-0002-7266-9868
authors.initials: J
authors.lastname: Kemmer
authors.affiliation: Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California, United States of America.|Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California, United States of America.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States of America.|Departments of Anatomy and Bioengineering and Therapeutic Sciences and Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California, United States of America.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Hwang
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California, United States of America.|Francis I. Proctor Foundation, University of California, San Francisco, California, United States of America.
authors.forename: Matilda F
authors.initials: MF
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004728:Endothelium, Corneal / Q000378:metabolism; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged