Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17
Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF) used to treat macular edema following branch retinal vein occlusion (BRVO). Despite well-documented efficacy, there is limited knowledge about proteome changes following aflibercept intervention in BRVO. Proteome changes may pr...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2021/6690260 |
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| author | Lasse Jørgensen Cehofski Anders Kruse Alexander Nørgård Alsing Benn Falch Sejergaard Jonas Ellegaard Nielsen Shona Pedersen Danson Vasanthan Muttuvelu Svend Kirkeby Bent Honoré Henrik Vorum |
| author_facet | Lasse Jørgensen Cehofski Anders Kruse Alexander Nørgård Alsing Benn Falch Sejergaard Jonas Ellegaard Nielsen Shona Pedersen Danson Vasanthan Muttuvelu Svend Kirkeby Bent Honoré Henrik Vorum |
| author_sort | Lasse Jørgensen Cehofski |
| collection | DOAJ |
| description | Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF) used to treat macular edema following branch retinal vein occlusion (BRVO). Despite well-documented efficacy, there is limited knowledge about proteome changes following aflibercept intervention in BRVO. Proteome changes may provide insights into mechanisms of action as well as aspects related to safety profile. In seven Danish Landrace pigs, BRVO was induced with a well-established experimental model of argon laser-induced BRVO. BRVO was induced in both eyes. Three days after the induced BRVO, aflibercept was injected intravitreally in the right eyes, while the left eyes received intravitreal isotonic saline water. Retinas were collected 15 days after the induced BRVO and analyzed with label-free quantification liquid chromatography tandem mass spectrometry (LFQ LC-MS/MS). Fourteen proteins were changed in expression following aflibercept intervention in the BRVO model. LFQ LC-MS/MS identified an upregulation of DnaJ homolog subfamily C member 17 (DNAJC17) (fold change = 6.19) and a modest downregulation of isoform 2 of the protein encoded by N-myc downstream regulated gene 2 (NDRG2) (fold change = 0.40). NDRG2 was unchanged by Western blotting. In the additional significantly regulated proteins, only discrete changes were observed (fold changes 0.52–1.59). Our study is the first to report an association between aflibercept intervention and the heat shock protein DNAJC17. Our results indicate that the role of heat shock proteins in the treatment of BRVO should be further explored. |
| format | Article |
| id | doaj-art-7ed43e36925d438e9ec9f181dab37c1f |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-7ed43e36925d438e9ec9f181dab37c1f2025-08-20T03:35:40ZengWileyJournal of Ophthalmology2090-004X2090-00582021-01-01202110.1155/2021/66902606690260Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17Lasse Jørgensen Cehofski0Anders Kruse1Alexander Nørgård Alsing2Benn Falch Sejergaard3Jonas Ellegaard Nielsen4Shona Pedersen5Danson Vasanthan Muttuvelu6Svend Kirkeby7Bent Honoré8Henrik Vorum9Department of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University Hospital, Aalborg, DenmarkDepartment of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Odontology, School of Dentistry, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Medicine, Aalborg University Hospital, Aalborg, DenmarkDepartment of Ophthalmology, Aalborg University Hospital, Aalborg, DenmarkAflibercept is an inhibitor of vascular endothelial growth factor (VEGF) used to treat macular edema following branch retinal vein occlusion (BRVO). Despite well-documented efficacy, there is limited knowledge about proteome changes following aflibercept intervention in BRVO. Proteome changes may provide insights into mechanisms of action as well as aspects related to safety profile. In seven Danish Landrace pigs, BRVO was induced with a well-established experimental model of argon laser-induced BRVO. BRVO was induced in both eyes. Three days after the induced BRVO, aflibercept was injected intravitreally in the right eyes, while the left eyes received intravitreal isotonic saline water. Retinas were collected 15 days after the induced BRVO and analyzed with label-free quantification liquid chromatography tandem mass spectrometry (LFQ LC-MS/MS). Fourteen proteins were changed in expression following aflibercept intervention in the BRVO model. LFQ LC-MS/MS identified an upregulation of DnaJ homolog subfamily C member 17 (DNAJC17) (fold change = 6.19) and a modest downregulation of isoform 2 of the protein encoded by N-myc downstream regulated gene 2 (NDRG2) (fold change = 0.40). NDRG2 was unchanged by Western blotting. In the additional significantly regulated proteins, only discrete changes were observed (fold changes 0.52–1.59). Our study is the first to report an association between aflibercept intervention and the heat shock protein DNAJC17. Our results indicate that the role of heat shock proteins in the treatment of BRVO should be further explored.http://dx.doi.org/10.1155/2021/6690260 |
| spellingShingle | Lasse Jørgensen Cehofski Anders Kruse Alexander Nørgård Alsing Benn Falch Sejergaard Jonas Ellegaard Nielsen Shona Pedersen Danson Vasanthan Muttuvelu Svend Kirkeby Bent Honoré Henrik Vorum Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 Journal of Ophthalmology |
| title | Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 |
| title_full | Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 |
| title_fullStr | Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 |
| title_full_unstemmed | Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 |
| title_short | Aflibercept Intervention in Experimental Branch Retinal Vein Occlusion Results in Upregulation of DnaJ Homolog Subfamily C Member 17 |
| title_sort | aflibercept intervention in experimental branch retinal vein occlusion results in upregulation of dnaj homolog subfamily c member 17 |
| url | http://dx.doi.org/10.1155/2021/6690260 |
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