NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats
Among the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the admin...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/20/3246 |
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| author | Elena Fico Pamela Rosso Viviana Triaca Marco Segatto Alessandro Lambiase Paola Tirassa |
| author_facet | Elena Fico Pamela Rosso Viviana Triaca Marco Segatto Alessandro Lambiase Paola Tirassa |
| author_sort | Elena Fico |
| collection | DOAJ |
| description | Among the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the administration of eye drops containing NGF (ed-NGF) to adult Sprague Dawley rats receiving streptozotocin (STZ) intraperitoneal injection was used as an experimental paradigm to investigate NGF modulation of VEGFA and its receptor VEGFR2 expression. We show that ed-NGF treatment prevents the histological and vascular alterations in STZ retina, VEGFR2 expression decreased in GCL and INL, and preserved the co-expression of VEGFR2 and NGF-tropomyosin-related kinase A (TrkA) receptor in retinal ganglion cells (RGCs). The WB analysis confirmed the NGF effect on VEGFR2 expression and activation, and showed a recovery of VEGF isoform dysregulation by suppressing STZ-induced VEGFA<sub>121</sub> expression. Reduction in inflammatory and pro-apoptotic intracellular signals were also found in STZ+NGF retina. These findings suggest that ed-NGF administration might favor neuroretina protection, and in turn counteract the vascular impairment by regulating VEGFR2 and/or VEGFA isoform expression during the early stages of the disease. The possibility that an increase in the NGF availability might contribute to the switch from the proangiogenic/apoptotic to the neuroprotective action of VEGF is discussed. |
| first_indexed | 2024-03-09T20:29:02Z |
| format | Article |
| id | doaj.art-505bec0773ae4456b1d226b715314029 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:29:02Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-505bec0773ae4456b1d226b7153140292023-11-23T23:27:56ZengMDPI AGCells2073-44092022-10-011120324610.3390/cells11203246NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic RatsElena Fico0Pamela Rosso1Viviana Triaca2Marco Segatto3Alessandro Lambiase4Paola Tirassa5Institute of Biochemistry and Cell Biology, National Research Council (CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council (CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council (CNR), International Campus A. Buzzati Traverso, Via E. Ramarini 32, Monterotondo, 00015 Rome, ItalyDepartment of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, 86090 Pesche, ItalyDepartment of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyInstitute of Biochemistry and Cell Biology, National Research Council (CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyAmong the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the administration of eye drops containing NGF (ed-NGF) to adult Sprague Dawley rats receiving streptozotocin (STZ) intraperitoneal injection was used as an experimental paradigm to investigate NGF modulation of VEGFA and its receptor VEGFR2 expression. We show that ed-NGF treatment prevents the histological and vascular alterations in STZ retina, VEGFR2 expression decreased in GCL and INL, and preserved the co-expression of VEGFR2 and NGF-tropomyosin-related kinase A (TrkA) receptor in retinal ganglion cells (RGCs). The WB analysis confirmed the NGF effect on VEGFR2 expression and activation, and showed a recovery of VEGF isoform dysregulation by suppressing STZ-induced VEGFA<sub>121</sub> expression. Reduction in inflammatory and pro-apoptotic intracellular signals were also found in STZ+NGF retina. These findings suggest that ed-NGF administration might favor neuroretina protection, and in turn counteract the vascular impairment by regulating VEGFR2 and/or VEGFA isoform expression during the early stages of the disease. The possibility that an increase in the NGF availability might contribute to the switch from the proangiogenic/apoptotic to the neuroprotective action of VEGF is discussed.https://www.mdpi.com/2073-4409/11/20/3246NGFVEGFTrkAeye dropsstreptozotocindiabetic retinopathy |
| spellingShingle | Elena Fico Pamela Rosso Viviana Triaca Marco Segatto Alessandro Lambiase Paola Tirassa NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats Cells NGF VEGF TrkA eye drops streptozotocin diabetic retinopathy |
| title | NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats |
| title_full | NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats |
| title_fullStr | NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats |
| title_full_unstemmed | NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats |
| title_short | NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats |
| title_sort | ngf prevents loss of trka vegfr2 cells and vegf isoform dysregulation in the retina of adult diabetic rats |
| topic | NGF VEGF TrkA eye drops streptozotocin diabetic retinopathy |
| url | https://www.mdpi.com/2073-4409/11/20/3246 |
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