Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy.
Adult
Aged
Aged, 80 and over
Apolipoproteins E
/ genetics
Carrier Proteins
/ genetics
Chromatography, High Pressure Liquid
Female
Fuchs' Endothelial Dystrophy
/ genetics
Gene Expression Regulation
/ physiology
Humans
Immunohistochemistry
Male
Mass Spectrometry
Middle Aged
Proteomics
RNA, Messenger
/ genetics
Real-Time Polymerase Chain Reaction
Fuchs endothelial corneal dystrophy
apolipoproteins E
immunoglobulin heavy constant gamma 1 protein
proteomics
real-time polymerase chain reaction
Journal
Clinical & experimental ophthalmology
ISSN: 1442-9071
Titre abrégé: Clin Exp Ophthalmol
Pays: Australia
ID NLM: 100896531
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
01
01
2019
revised:
30
05
2019
accepted:
05
06
2019
pubmed:
18
6
2019
medline:
1
12
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane. Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MS Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis. This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.
Sections du résumé
BACKGROUND
BACKGROUND
Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane.
METHODS
METHODS
Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MS
RESULTS
RESULTS
Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis.
CONCLUSIONS
CONCLUSIONS
This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.
Substances chimiques
ApoE protein, human
0
Apolipoproteins E
0
Carrier Proteins
0
RNA, Messenger
0
prolactin-binding protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1028-1042Subventions
Organisme : Flinders Medical Centre Foundation
Organisme : Ophthalmic Research Institute of Australia
Informations de copyright
© 2019 Royal Australian and New Zealand College of Ophthalmologists.
Références
Adamis AP, Filatov V, Tripathi BJ, Tripathi RC. Fuchs' endothelial dystrophy of the cornea. Surv Ophthalmol. 1993;38(2):149-168.
Kenney MC, Labermeier U, Hinds D, Waring GO 3rd. Characterization of the Descemet's membrane/posterior collagenous layer isolated from Fuchs' endothelial dystrophy corneas. Exp Eye Res. 1984;39(3):267-277.
Price MO, Gorovoy M, Benetz BA, et al. Descemet's stripping automated endothelial keratoplasty outcomes compared with penetrating keratoplasty from the cornea donor study. Ophthalmology. 2010;117(3):438-444.
Riazuddin SA, Zaghloul NA, Al-Saif A, et al. Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact with FCD4 on chromosome 9p. Am J Hum Genet. 2010;86(1):45-53.
Santo RM, Yamaguchi T, Kanai A, Okisaka S, Nakajima A. Clinical and histopathologic features of corneal dystrophies in Japan. Ophthalmology. 1995;102(4):557-567.
Omar N, Bou Chacra CT, Tabbara KF. Outcome of corneal transplantation in a private institution in Saudi Arabia. Clin Ophthalmol. 2013;7:1311-1318.
Williams KA, Keane MC, Galettis RA, Jones VJ, Mills RAD, Coster DJ. The Australian Corneal Graft Registry 2015 Report. Adelaide, Australia: Flinders University; 2015.
Vithana EN, Morgan PE, Ramprasad V, et al. SLC4A11 mutations in Fuchs endothelial corneal dystrophy. Hum Mol Genet. 2008;17(5):656-666.
Baratz KH, Tosakulwong N, Ryu E, et al. E2-2 protein and Fuchs's corneal dystrophy. N Engl J Med. 2010;363(11):1016-1024.
Riazuddin SA, Parker DS, McGlumphy EJ, et al. Mutations in LOXHD1, a recessive-deafness locus, cause dominant late-onset Fuchs corneal dystrophy. Am J Hum Genet. 2012;90(3):533-539.
Biswas S, Munier FL, Yardley J, et al. Missense mutations in COL8A2, the gene encoding the α2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum Mol Genet. 2001;10(21):2415-2423.
Riazuddin SA, Vithana EN, Seet L-F, et al. Missense mutations in the sodium borate cotransporter SLC4A11 cause late-onset Fuchs corneal dystrophya. Hum Mutat. 2010;31(11):1261-1268.
Wieben ED, Aleff RA, Tosakulwong N, et al. A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS One. 2012;7(11):e49083.
Afshari NA, Igo RP Jr, Morris NJ, et al. Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy. Nat Commun. 2017;8:14898.
Jurkunas UV, Bitar MS, Funaki T, Azizi B. Evidence of oxidative stress in the pathogenesis of fuchs endothelial corneal dystrophy. Am J Pathol. 2010;177(5):2278-2289.
Engler C, Kelliher C, Spitze AR, Speck CL, Eberhart CG, Jun AS. Unfolded protein response in fuchs endothelial corneal dystrophy: a unifying pathogenic pathway? Am J Ophthalmol. 2010;149(2):194-202.e2.
Borderie VM, Baudrimont M, Vallée A, Ereau TL, Gray F, Laroche L. Corneal endothelial cell apoptosis in patients with Fuchs' dystrophy. Invest Ophthalmol Vis Sci. 2000;41(9):2501-2505.
Czarny P, Kasprzak E, Wielgorski M, et al. DNA damage and repair in Fuchs endothelial corneal dystrophy. Mol Biol Rep. 2013;40(4):2977-2983.
Meng H, Matthaei M, Ramanan N, et al. L450W and Q455K Col8a2 knock-in mouse models of Fuchs endothelial corneal dystrophy show distinct phenotypes and evidence for altered autophagy. Invest Ophthalmol Vis Sci. 2013;54(3):1887-1897.
Jurkunas UV, Bitar M, Rawe I. Colocalization of increased transforming growth factor-beta-induced protein (TGFBIp) and Clusterin in Fuchs endothelial corneal dystrophy. Invest Ophthalmol Vis Sci. 2009;50(3):1129-1136.
Wyatt A, Yerbury J, Poon S, Dabbs R, Wilson M. Chapter 6: the chaperone action of Clusterin and its putative role in quality control of extracellular protein folding. Adv Cancer Res. 2009;104:89-114.
Kim JE, Kim SJ, Lee BH, Park RW, Kim KS, Kim IS. Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, betaig-h3. J Biol Chem. 2000;275(40):30907-30915.
Louttit MD, Kopplin LJ, Igo RP, et al. A multi-center study to map genes for Fuchs' endothelial corneal dystrophy: baseline characteristics and heritability. Cornea. 2012;31(1):26-35.
Krachmer JH, Purcell JJ Jr, Young CW, Bucher KD. Corneal endothelial dystrophy. A study of 64 families. Arch Ophthalmol. 1978;96(11):2036-2039.
Pieroni L, Finamore F, Ronci M, et al. Proteomics investigation of human platelets in healthy donors and cystic fibrosis patients by shotgun nUPLC-MSE and 2DE: a comparative study. Mol Biosyst. 2011;7(3):630-639.
Vissers JP, Langridge JI, Aerts JM. Analysis and quantification of diagnostic serum markers and protein signatures for Gaucher disease. Mol Cell Proteomics. 2007;6(5):755-766.
Silva JC, Denny R, Dorschel CA, et al. Quantitative proteomic analysis by accurate mass retention time pairs. Anal Chem. 2005;77(7):2187-2200.
Kuot A, Hewitt AW, Griggs K, et al. Association of TCF4 and CLU polymorphisms with Fuchs' endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. Eur J Hum Genet. 2012;20(6):632-638.
Simon P. Q-Gene: processing quantitative real-time RT-PCR data. Bioinformatics. 2003;19(11):1439-1440.
Lynn DJ, Winsor GL, Chan C, et al. InnateDB: facilitating systems-level analyses of the mammalian innate immune response. Mol Syst Biol. 2008;4:218.
Weller JM, Zenkel M, Schlötzer-Schrehardt U, Bachmann BO, Tourtas T, Kruse FE. Extracellular matrix alterations in late-onset Fuchs' corneal dystrophy. Invest Ophthalmol Vis Sci. 2014;55(6):3700-3708.
Wieben ED, Aleff RA, Tang X, et al. Trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene leads to widespread mRNA splicing changes in Fuchs' endothelial corneal dystrophy. Invest Ophthalmol Vis Sci. 2017;58(1):343-352.
Jurkunas UV, Rawe I, Bitar MS, et al. Decreased expression of peroxiredoxins in Fuchs' endothelial dystrophy. Invest Ophthalmol Vis Sci. 2008;49(7):2956-2963.
Poulsen ET, Dyrlund TF, Runager K, et al. Proteomics of Fuchs' endothelial corneal dystrophy support that the extracellular matrix of Descemet's membrane is disordered. J Proteome Res. 2014;13:4659-4667.
Johnson DH, Bourne WM, Campbell RJ. The ultrastructure of Descemet's membrane: I. Changes with age in normal corneas. Arch Ophthalmol. 1982;100(12):1942-1947.
Waring GO 3rd. Posterior collagenous layer of the cornea. Ultrastructural classification of abnormal collagenous tissue posterior to Descemet's membrane in 30 cases. Arch Ophthalmol. 1982;100(1):122-134.
Bourne WM. Biology of the corneal endothelium in health and disease. Eye. 2003;17(8):912-918.
Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases. Neurobiol Dis. 2014;72PA:3-12.
Tudorache IF, Trusca VG, Gafencu AV. Apolipoprotein E-a multifunctional protein with implications in various pathologies as a result of its structural features. Comput Struct Biotechnol J. 2017;15:359-365.
Niu N, Zhang J, Guo Y, Zhao Y, Korteweg C, Gu J. Expression and distribution of immunoglobulin G and its receptors in the human nervous system. Int J Biochem Cell Biol. 2011;43(4):556-563.
Pan B, Zheng S, Liu C, Xu Y. Suppression of IGHG1 gene expression by siRNA leads to growth inhibition and apoptosis induction in human prostate cancer cell. Mol Biol Rep. 2013;40(1):27-33.
Li X, Ni R, Chen J, et al. The presence of IGHG1 in human pancreatic carcinomas is associated with immune evasion mechanisms. Pancreas. 2011;40(5):753-761.
Qiu Y, Korteweg C, Chen Z, et al. Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer. Mod Pathol. 2012;25(1):36-45.
Weisgraber KH. Apolipoprotein E: structure-function relationships. Adv Protein Chem. 1994;45:249-302.
Libeu CP, Lund-Katz S, Phillips MC, et al. New insights into the heparan sulfate proteoglycan-binding activity of apolipoprotein E. J Biol Chem. 2001;276(42):39138-39144.
Hui DY, Basford JE. Distinct signaling mechanisms for apoE inhibition of cell migration and proliferation. Neurobiol Aging. 2005;26(3):317-323.
Huang DY, Weisgraber KH, Strittmatter WJ, Matthew WD. Interaction of apolipoprotein E with laminin increases neuronal adhesion and alters neurite morphology. Exp Neurol. 1995;136(2):251-257.
Allan LL, Hoefl K, Zheng DJ, et al. Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Blood. 2009;114(12):2411-2416.
Methia N, André P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD. ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med. 2001;7(12):810-815.
Fust A, Csuka D, Imre L, et al. The role of complement activation in the pathogenesis of Fuchs' dystrophy. Mol Immunol. 2014;58(2):177-181.