Dataset Information

Protein accumulation post-LASIK surgery in granular corneal dystrophy type II patients involves altered proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

ABSTRACT: his study present the protein profile of diseased cornea from granular corneal dystrophy patients developing protein accumulation after LASIK surgery. Extracted ion chromatography (XIC) label free quantification was perform using Mascot Distiller software. In addition, 2D-PAGE followed by western blot against the mutated protein TGFBIp that cause the protein accumulation in the cornea, was examined and compared to normal corneal tissue.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr Jan Johannes Enghild

PROVIDER: MSV000080219 | MassIVE | Tue Oct 04 13:28:00 BST 2016

SECONDARY ACCESSION(S): PXD001997

REPOSITORIES: MassIVE

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Publications

LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp).

Poulsen Ebbe Toftgaard ET Nielsen Nadia Sukusu NS Jensen Morten M MM Nielsen Esben E Hjortdal Jesper J Kim Eung Kweon EK Enghild Jan J JJ

Proteomics 20160103 3

More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much l ...[more]

PMID: 26864644

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Project description: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

Dataset Information

Protein accumulation post-LASIK surgery in granular corneal dystrophy type II patients involves altered proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

Publications

LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp).

Similar Datasets

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