Proteomics reveals a set of highly enriched proteins in epiretinal membrane compared with inner limiting membrane

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  • Christos Christakopoulos
  • ,
  • Lasse Jørgensen Cehofski
  • ,
  • Steen Rugaard Christensen, Department of Ophthalmology, Zealand University Hospital, Næstved, Denmark., Denmark
  • Henrik Vorum, Øjensygdomme, Det Sundhedsvidenskabelige Fakultet, Klinik Hoved-Orto, Klinisk Institut, Aalborg Universitetshospital, Denmark
  • Bent Honoré

Few data exist regarding the protein composition of idiopathic epiretinal membrane (iERM). In the present study we compared the proteome of epiretinal membrane of iERM with the proteome of the inner limiting membrane (ILM) of idiopathic macular hole (iMH). Twelve epiretinal membrane samples were obtained from patients with iERM undergoing therapeutic vitrectomy. Twelve ILM samples were obtained from patients with iMH and were used as controls. Proteomic analysis was conducted with discovery-based label-free quantitative nano-liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). Verification of results was performed with targeted MS using selected reaction monitoring on a different set of samples. Discovery data were searched against the Uniprot Homo sapiens protein database using MaxQuant Software. Identified proteins were filtered with Perseus software. Bioinformatic analysis of the differences in protein expression between epiretinal membrane from iERM and ILM from iMH was performed using STRING. A total of 2,183 different proteins were identified. 357 proteins were found to be present in all samples. The protein profile of epiretinal membrane was highly different from ILM with 62 proteins found in significantly higher concentration in epiretinal membrane. The proteins up-regulated more than 10-fold in epiretinal membrane were: fibrillin-1, tenascin, prolargin, biglycan, opticin, collagen alpha-1(II) chain, protein-glutamine gamma-glutamyltransferase 2, fibronectin, filamin-A, collagen alpha-2(IX) chain, spectrin alpha chain, transforming growth factor beta induced protein ig-h3, dihydropyrimidinase - related protein 3, endoplasmin and glutamate dehydrogenase 1. Proteins with high level in epiretinal membrane consisted of proteins that especially localized to the actin cytoskeleton, the extracellular matrix and the mitochondrion. Analysis of all proteins indicated that the disease process at least in part can be characterized as skin formation with perturbation of nucleotide metabolism. Epiretinal membrane mainly consists of an additional set of proteins than ILM. Our study identified proteins that have not earlier been associated with epiretinal membrane. Fifteen are found at very high concentration, 10-fold or more, and amongst these four proteins, fibrillin-1, tenascin, prolargin and biglycan are found at more than a 100-fold higher concentration. These proteins may be potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD014286.

Original languageEnglish
JournalExperimental Eye Research
Pages (from-to)107722
ISSN0014-4835
DOIs
Publication statusE-pub ahead of print - 11 Jul 2019

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