Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways
Purpose: To analyze and describe the proteome of the vitreous humour in eyes with idiopathic macular holes. Methods: We performed mass spectrometry (MS)-based label-free quantitative analysis of the vitreous proteome of idiopathic macular hole (IMH) and control donor vitreous. Comparative quantifi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Indian Journal of Ophthalmology |
| Subjects: | |
| Online Access: | http://www.ijo.in/article.asp?issn=0301-4738;year=2023;volume=71;issue=5;spage=2027;epage=2040;aulast=Sen |
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| author | Sagnik Sen Prithviraj Udaya Jayapal J Maheshwari Kim Ramasamy Naresh B Kannan Kuppamuthu Dharmalingam |
| author_facet | Sagnik Sen Prithviraj Udaya Jayapal J Maheshwari Kim Ramasamy Naresh B Kannan Kuppamuthu Dharmalingam |
| author_sort | Sagnik Sen |
| collection | DOAJ |
| description | Purpose: To analyze and describe the proteome of the vitreous humour in eyes with idiopathic macular holes. Methods: We performed mass spectrometry (MS)-based label-free quantitative analysis of the vitreous proteome of idiopathic macular hole (IMH) and control donor vitreous. Comparative quantification was performed using SCAFFOLD software which calculated fold changes of differential expression. Bioinformatics analysis was performed using DAVID and STRING software. Results: A total of 448 proteins were identified by LC-MS/MS in IMH and cadaveric eye vitreous samples, of which 199 proteins were common. IMH samples had 189 proteins that were unique and 60 proteins were present only in the control cadaveric vitreous. We found upregulation of several extracellular matrix (ECM) and cytoskeletal proteins, namely collagen alpha-1 (XVIII) chain, N-cadherin, EFEMP1/fibulin-3, basement membrane-specific heparan sulfate proteoglycan core protein, and target of Nesh-3. Several cytoskeleton proteins, namely tubulin, actin, and fibronectin levels, were significantly lower in IMH vitreous, probably reflecting increased ECM degradation. IMH vitreous also had a downregulation of unfolded protein response-mediated-mediated apoptosis proteins, possibly related to a state of increased cell survival and proliferation, along with a remodelling and aberrant production of ECM contents. Conclusion: The pathogenesis of macular holes may involve ECM remodelling, epithelial–mesenchymal transformation, downregulation of apoptosis, protein folding defects, and complement pathway. The vitreo-retinal milieu in macular holes contain molecules related to both ECM degradation and inhibition of the same, thereby maintaining a homeostasis. |
| first_indexed | 2024-03-12T22:30:21Z |
| format | Article |
| id | doaj.art-3078a67f08304fa3b37762afc46d501a |
| institution | Directory Open Access Journal |
| issn | 0301-4738 1998-3689 |
| language | English |
| last_indexed | 2024-03-12T22:30:21Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Ophthalmology |
| spelling | doaj.art-3078a67f08304fa3b37762afc46d501a2023-07-21T15:14:10ZengWolters Kluwer Medknow PublicationsIndian Journal of Ophthalmology0301-47381998-36892023-01-017152027204010.4103/ijo.IJO_2068_22Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathwaysSagnik SenPrithviraj UdayaJayapal J MaheshwariKim RamasamyNaresh B KannanKuppamuthu DharmalingamPurpose: To analyze and describe the proteome of the vitreous humour in eyes with idiopathic macular holes. Methods: We performed mass spectrometry (MS)-based label-free quantitative analysis of the vitreous proteome of idiopathic macular hole (IMH) and control donor vitreous. Comparative quantification was performed using SCAFFOLD software which calculated fold changes of differential expression. Bioinformatics analysis was performed using DAVID and STRING software. Results: A total of 448 proteins were identified by LC-MS/MS in IMH and cadaveric eye vitreous samples, of which 199 proteins were common. IMH samples had 189 proteins that were unique and 60 proteins were present only in the control cadaveric vitreous. We found upregulation of several extracellular matrix (ECM) and cytoskeletal proteins, namely collagen alpha-1 (XVIII) chain, N-cadherin, EFEMP1/fibulin-3, basement membrane-specific heparan sulfate proteoglycan core protein, and target of Nesh-3. Several cytoskeleton proteins, namely tubulin, actin, and fibronectin levels, were significantly lower in IMH vitreous, probably reflecting increased ECM degradation. IMH vitreous also had a downregulation of unfolded protein response-mediated-mediated apoptosis proteins, possibly related to a state of increased cell survival and proliferation, along with a remodelling and aberrant production of ECM contents. Conclusion: The pathogenesis of macular holes may involve ECM remodelling, epithelial–mesenchymal transformation, downregulation of apoptosis, protein folding defects, and complement pathway. The vitreo-retinal milieu in macular holes contain molecules related to both ECM degradation and inhibition of the same, thereby maintaining a homeostasis.http://www.ijo.in/article.asp?issn=0301-4738;year=2023;volume=71;issue=5;spage=2027;epage=2040;aulast=Sendonor vitreousmacular holemass spectrometrypathogenesisproteomics |
| spellingShingle | Sagnik Sen Prithviraj Udaya Jayapal J Maheshwari Kim Ramasamy Naresh B Kannan Kuppamuthu Dharmalingam Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways Indian Journal of Ophthalmology donor vitreous macular hole mass spectrometry pathogenesis proteomics |
| title | Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways |
| title_full | Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways |
| title_fullStr | Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways |
| title_full_unstemmed | Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways |
| title_short | Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial–mesenchymal transformation and unfolded protein-response pathways |
| title_sort | profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling epithelial mesenchymal transformation and unfolded protein response pathways |
| topic | donor vitreous macular hole mass spectrometry pathogenesis proteomics |
| url | http://www.ijo.in/article.asp?issn=0301-4738;year=2023;volume=71;issue=5;spage=2027;epage=2040;aulast=Sen |
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