Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement
Abstract Proliferative diabetic retinopathy (PDR) is a sight-threatening diabetic complication in urgent need of new therapies. In this study we identify potential molecular mechanisms and target candidates in the pathogenesis of PDR fibrovascular tissue formation. We performed mRNA sequencing of RN...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97970-5 |
| _version_ | 1818572989059301376 |
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| author | Ani Korhonen Erika Gucciardo Kaisa Lehti Sirpa Loukovaara |
| author_facet | Ani Korhonen Erika Gucciardo Kaisa Lehti Sirpa Loukovaara |
| author_sort | Ani Korhonen |
| collection | DOAJ |
| description | Abstract Proliferative diabetic retinopathy (PDR) is a sight-threatening diabetic complication in urgent need of new therapies. In this study we identify potential molecular mechanisms and target candidates in the pathogenesis of PDR fibrovascular tissue formation. We performed mRNA sequencing of RNA isolated from eleven excised fibrovascular membranes of type 1 diabetic PDR patients and two non-diabetic patients with rhegmatogenous retinal detachment with proliferative vitreoretinopathy. We determined differentially expressed genes between these groups and performed pathway and gene ontology term enrichment analyses to identify potential underlying mechanisms, pathways, and regulators. Multiple pro-angiogenic processes, including VEGFA-dependent and -independent pathways, as well as processes related to lymphatic development, epithelial to mesenchymal transition (EMT), wound healing, inflammation, fibrosis, and extracellular matrix (ECM) composition, were overrepresented in PDR. Overrepresentation of different angiogenic processes may help to explain the transient nature of the benefits that many patients receive from current intravitreal anti-angiogenic therapies, highlighting the importance of combinatorial treatments. Enrichment of genes and pathways related to lymphatic development indicates that targeting lymphatic involvement in PDR progression could have therapeutic relevance. Together with overrepresentation of EMT and fibrosis as well as differential ECM composition, these findings demonstrate the complexity of PDR fibrovascular tissue formation and provide avenues for the development of novel treatments. |
| first_indexed | 2024-12-15T00:05:06Z |
| format | Article |
| id | doaj.art-c440f4706bf64f2da2bd005227c210ce |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-15T00:05:06Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c440f4706bf64f2da2bd005227c210ce2022-12-21T22:42:45ZengNature PortfolioScientific Reports2045-23222021-09-0111111410.1038/s41598-021-97970-5Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvementAni Korhonen0Erika Gucciardo1Kaisa Lehti2Sirpa Loukovaara3Individualized Drug Therapy Research Program, Faculty of Medicine, University of HelsinkiIndividualized Drug Therapy Research Program, Faculty of Medicine, University of HelsinkiIndividualized Drug Therapy Research Program, Faculty of Medicine, University of HelsinkiIndividualized Drug Therapy Research Program, Faculty of Medicine, University of HelsinkiAbstract Proliferative diabetic retinopathy (PDR) is a sight-threatening diabetic complication in urgent need of new therapies. In this study we identify potential molecular mechanisms and target candidates in the pathogenesis of PDR fibrovascular tissue formation. We performed mRNA sequencing of RNA isolated from eleven excised fibrovascular membranes of type 1 diabetic PDR patients and two non-diabetic patients with rhegmatogenous retinal detachment with proliferative vitreoretinopathy. We determined differentially expressed genes between these groups and performed pathway and gene ontology term enrichment analyses to identify potential underlying mechanisms, pathways, and regulators. Multiple pro-angiogenic processes, including VEGFA-dependent and -independent pathways, as well as processes related to lymphatic development, epithelial to mesenchymal transition (EMT), wound healing, inflammation, fibrosis, and extracellular matrix (ECM) composition, were overrepresented in PDR. Overrepresentation of different angiogenic processes may help to explain the transient nature of the benefits that many patients receive from current intravitreal anti-angiogenic therapies, highlighting the importance of combinatorial treatments. Enrichment of genes and pathways related to lymphatic development indicates that targeting lymphatic involvement in PDR progression could have therapeutic relevance. Together with overrepresentation of EMT and fibrosis as well as differential ECM composition, these findings demonstrate the complexity of PDR fibrovascular tissue formation and provide avenues for the development of novel treatments.https://doi.org/10.1038/s41598-021-97970-5 |
| spellingShingle | Ani Korhonen Erika Gucciardo Kaisa Lehti Sirpa Loukovaara Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement Scientific Reports |
| title | Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement |
| title_full | Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement |
| title_fullStr | Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement |
| title_full_unstemmed | Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement |
| title_short | Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement |
| title_sort | proliferative diabetic retinopathy transcriptomes reveal angiogenesis anti angiogenic therapy escape mechanisms fibrosis and lymphatic involvement |
| url | https://doi.org/10.1038/s41598-021-97970-5 |
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