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| Status |
Public on Feb 04, 2017 |
| Title |
Comprehensive characterization of DNA methylation changes in Fuchs Endothelial Corneal Dystrophy |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
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 unkonwn. Here, we report on and compare the DNA methyhlation 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
Methylation of DNA is a key epigenetic mark that occurs in aging tissues. Altered DNA methlyation patterns have been observed in several late onset, and progressive ocular diseases including macular degeneration, glaucoma, and cataracts. While DNA methylation changes also occur in the common, late onset corneal dystrophy, FECD, has not been previously studied. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indicatioin for corneal transplantation in developed countries. Our study examined and compared the genome-scale DNA methylation profiels of corneal endothelial tissue from normal control and 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 findings suggest that alterations in DNA methylation may contribute to FECD pathogenesis by modifying the expression of genes with critical biological roles in the corneal endothelium. Our study has important clinical implications as FECD is a leading indication for corneal transplantationin the geriatric population. The effective medical treatment of FECD is a major unmet clinical challenge. Our findings suggest altered DNA methylation as a novel candidate therapeutic target in FECD
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| Overall design |
Illumina Infinium HumanMethylation450 DNA methylation array: 15 cases (9 used), 4 control
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| Contributor(s) |
Khuc E, Bainer R, Wolf M, Clay SM, Weisenberger DJ, Kemmer J, Weaver VM, Hwang DG, Chan MF |
| Citation(s) |
31705138 |
| Submission date |
Feb 03, 2017 |
| Last update date |
Nov 19, 2019 |
| Contact name |
Selene Clay |
| Organization name |
University of California, San Francisco
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| Department |
Ophthalmology
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| Lab |
Matilda Chan
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| Street address |
1001 Potrero Ave Rm 210
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| City |
San Francisco |
| State/province |
California |
| ZIP/Postal code |
94110 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA369763 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94462_Fuchs_M-value_matrix.txt.gz |
42.1 Mb |
(ftp)(http) |
TXT |
| GSE94462_RAW.tar |
312.9 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data are available on Series record |
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