Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach
Background and Purpose Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal dam...
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| Published in | British journal of pharmacology Vol. 176; no. 13; pp. 2179 - 2194 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Blackwell Publishing Ltd
01.07.2019
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Background and Purpose
Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs–mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy.
Methods
A focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA‐Cytoscape). Identification of miRNAs–mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real‐time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs.
Key Results
We found that miR‐20a‐5p, miR‐20a‐3p, miR‐20b, miR‐106a‐5p, miR‐27a‐5p, miR‐27b‐3p, miR‐206‐3p, and miR‐381‐3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain‐derived neurotrophic factor (BDNF), PPAR‐α, and cAMP response element‐binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice.
Conclusions and Implications
Serum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR‐α, and CREB1, before vasculopathy in diabetic retinas. |
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| AbstractList | Background and PurposeDiabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs–mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy.MethodsA focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA‐Cytoscape). Identification of miRNAs–mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real‐time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs.Key ResultsWe found that miR‐20a‐5p, miR‐20a‐3p, miR‐20b, miR‐106a‐5p, miR‐27a‐5p, miR‐27b‐3p, miR‐206‐3p, and miR‐381‐3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain‐derived neurotrophic factor (BDNF), PPAR‐α, and cAMP response element‐binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice.Conclusions and ImplicationsSerum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR‐α, and CREB1, before vasculopathy in diabetic retinas. Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs-mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy. A focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA-Cytoscape). Identification of miRNAs-mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real-time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs. We found that miR-20a-5p, miR-20a-3p, miR-20b, miR-106a-5p, miR-27a-5p, miR-27b-3p, miR-206-3p, and miR-381-3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain-derived neurotrophic factor (BDNF), PPAR-α, and cAMP response element-binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice. Serum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR-α, and CREB1, before vasculopathy in diabetic retinas. Background and Purpose Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs–mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy. Methods A focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA‐Cytoscape). Identification of miRNAs–mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real‐time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs. Key Results We found that miR‐20a‐5p, miR‐20a‐3p, miR‐20b, miR‐106a‐5p, miR‐27a‐5p, miR‐27b‐3p, miR‐206‐3p, and miR‐381‐3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain‐derived neurotrophic factor (BDNF), PPAR‐α, and cAMP response element‐binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice. Conclusions and Implications Serum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR‐α, and CREB1, before vasculopathy in diabetic retinas. Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs-mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy.BACKGROUND AND PURPOSEDiabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects. Therefore, we aimed at identification of dysregulated miRNAs-mRNA interactions that might be biomarkers and pharmacological targets for diagnosis and treatment of early diabetic retinopathy.A focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA-Cytoscape). Identification of miRNAs-mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real-time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs.METHODSA focused set of miRNAs was predicted through a bioinformatic analysis accessing to Gene Expression Omnibus dataset and enrichment of information approach (GENEMANIA-Cytoscape). Identification of miRNAs-mRNA interactions was carried out with miRNET analysis. Diabetes was induced in C57BL6J mice by streptozotocin and samples analysed at 5 and 10 weeks after diabetes induction. Retinal ultrastructure of diabetic mice was analysed through electron microscopy. We used Real-time PCR, western blot analysis, elisa, and immunohistochemistry to study expression of miRNAs and possible targets of dysregulated miRNAs.We found that miR-20a-5p, miR-20a-3p, miR-20b, miR-106a-5p, miR-27a-5p, miR-27b-3p, miR-206-3p, and miR-381-3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain-derived neurotrophic factor (BDNF), PPAR-α, and cAMP response element-binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice.KEY RESULTSWe found that miR-20a-5p, miR-20a-3p, miR-20b, miR-106a-5p, miR-27a-5p, miR-27b-3p, miR-206-3p, and miR-381-3p were dysregulated in the retina and serum of diabetic mice. VEGF, brain-derived neurotrophic factor (BDNF), PPAR-α, and cAMP response element-binding protein 1 (CREB1) are targets of dysregulated miRNAs, which then modulated protein expression in diabetic retina. We found structural modifications in retinas from diabetic mice.Serum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR-α, and CREB1, before vasculopathy in diabetic retinas.CONCLUSIONS AND IMPLICATIONSSerum and retina of diabetic mice express eight dysregulated miRNAs, which modified the expression of VEGF, BDNF, PPAR-α, and CREB1, before vasculopathy in diabetic retinas. |
| Author | Bucolo, Claudio Trotta, Maria Consiglia Hermenean, Anca Platania, Chiara Bianca Maria D'Amico, Michele D'Amico, Giovanbattista Rossi, Settimio Panarese, Iacopo Herman, Hildegard Balta, Cornel Maisto, Rosa Gesualdo, Carlo Drago, Filippo Ferraraccio, Franca |
| AuthorAffiliation | 3 Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences University of Campania “Luigi Vanvitelli” Naples Italy 4 Institute of Life Sciences Vasile Godis Western University of Arad Arad Romania 1 Department of Biomedical and Biotechnological Sciences, School of Medicine University of Catania Catania Italy 2 Department of Experimental Medicine, Division of Pharmacology University of Campania “Luigi Vanvitelli” Naples Italy 6 Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “Luigi Vanvitelli” Naples Italy 5 Department of Biochemistry and Molecular Biology University of Bucharest Bucharest Romania 7 Center for Research in Ocular Pharmacology—CERFO University of Catania Catania Italy |
| AuthorAffiliation_xml | – name: 2 Department of Experimental Medicine, Division of Pharmacology University of Campania “Luigi Vanvitelli” Naples Italy – name: 3 Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences University of Campania “Luigi Vanvitelli” Naples Italy – name: 7 Center for Research in Ocular Pharmacology—CERFO University of Catania Catania Italy – name: 1 Department of Biomedical and Biotechnological Sciences, School of Medicine University of Catania Catania Italy – name: 5 Department of Biochemistry and Molecular Biology University of Bucharest Bucharest Romania – name: 4 Institute of Life Sciences Vasile Godis Western University of Arad Arad Romania – name: 6 Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “Luigi Vanvitelli” Naples Italy |
| Author_xml | – sequence: 1 givenname: Chiara Bianca Maria surname: Platania fullname: Platania, Chiara Bianca Maria organization: University of Catania – sequence: 2 givenname: Rosa surname: Maisto fullname: Maisto, Rosa organization: University of Campania “Luigi Vanvitelli” – sequence: 3 givenname: Maria Consiglia surname: Trotta fullname: Trotta, Maria Consiglia organization: University of Campania “Luigi Vanvitelli” – sequence: 4 givenname: Michele surname: D'Amico fullname: D'Amico, Michele organization: University of Campania “Luigi Vanvitelli” – sequence: 5 givenname: Settimio surname: Rossi fullname: Rossi, Settimio organization: University of Campania “Luigi Vanvitelli” – sequence: 6 givenname: Carlo surname: Gesualdo fullname: Gesualdo, Carlo organization: University of Campania “Luigi Vanvitelli” – sequence: 7 givenname: Giovanbattista surname: D'Amico fullname: D'Amico, Giovanbattista organization: Vasile Godis Western University of Arad – sequence: 8 givenname: Cornel surname: Balta fullname: Balta, Cornel organization: Vasile Godis Western University of Arad – sequence: 9 givenname: Hildegard surname: Herman fullname: Herman, Hildegard organization: Vasile Godis Western University of Arad – sequence: 10 givenname: Anca surname: Hermenean fullname: Hermenean, Anca organization: University of Bucharest – sequence: 11 givenname: Franca surname: Ferraraccio fullname: Ferraraccio, Franca organization: University of Campania “Luigi Vanvitelli” – sequence: 12 givenname: Iacopo surname: Panarese fullname: Panarese, Iacopo organization: University of Campania “Luigi Vanvitelli” – sequence: 13 givenname: Filippo surname: Drago fullname: Drago, Filippo organization: University of Catania – sequence: 14 givenname: Claudio orcidid: 0000-0002-4879-4140 surname: Bucolo fullname: Bucolo, Claudio email: claudio.bucolo@unict.it organization: University of Catania |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30883703$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Chiara Bianca Maria Platania, Rosa Maisto, and Maria Consiglia Trotta have contributed equally to the work. |
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Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is... Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases... Background and PurposeDiabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is... |
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| SubjectTerms | Animals Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Computer Simulation Cyclic AMP Response Element-Binding Protein - metabolism Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - metabolism Diabetic retinopathy Diabetic Retinopathy - blood Diabetic Retinopathy - genetics Diabetic Retinopathy - metabolism Electron microscopy Gene expression Immunohistochemistry Male Mice, Inbred C57BL MicroRNAs - blood MicroRNAs - metabolism miRNA Peroxisome proliferator-activated receptors PPAR alpha - metabolism Research Paper Research Papers Retina Retina - metabolism Retinopathy Streptozocin Ultrastructure Vascular diseases Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism |
| Title | Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach |
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