A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies
We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/1/50 |
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| author | Alicia Arranz-Romera Maria Hernandez Patricia Checa-Casalengua Alfredo Garcia-Layana Irene T. Molina-Martinez Sergio Recalde Michael J. Young Budd A. Tucker Rocío Herrero-Vanrell Patricia Fernandez-Robredo Irene Bravo-Osuna |
| author_facet | Alicia Arranz-Romera Maria Hernandez Patricia Checa-Casalengua Alfredo Garcia-Layana Irene T. Molina-Martinez Sergio Recalde Michael J. Young Budd A. Tucker Rocío Herrero-Vanrell Patricia Fernandez-Robredo Irene Bravo-Osuna |
| author_sort | Alicia Arranz-Romera |
| collection | DOAJ |
| description | We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs. |
| first_indexed | 2024-03-09T05:13:07Z |
| format | Article |
| id | doaj.art-838e65d3e55d473491960920b36130fe |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T05:13:07Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-838e65d3e55d473491960920b36130fe2023-12-03T12:47:18ZengMDPI AGPharmaceuticals1424-82472021-01-011415010.3390/ph14010050A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal PathologiesAlicia Arranz-Romera0Maria Hernandez1Patricia Checa-Casalengua2Alfredo Garcia-Layana3Irene T. Molina-Martinez4Sergio Recalde5Michael J. Young6Budd A. Tucker7Rocío Herrero-Vanrell8Patricia Fernandez-Robredo9Irene Bravo-Osuna10Pharmaceutical Innovation in Ophthalmology (InnOftal), Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza de Ramón y Cajal, s/n, 28040 Madrid, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, 31008 Pamplona, SpainPharmaceutical Innovation in Ophthalmology (InnOftal), Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza de Ramón y Cajal, s/n, 28040 Madrid, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, 31008 Pamplona, SpainPharmaceutical Innovation in Ophthalmology (InnOftal), Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza de Ramón y Cajal, s/n, 28040 Madrid, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Harvard University, 20 Staniford Street, Boston, MA 02114, USAInstitute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USAPharmaceutical Innovation in Ophthalmology (InnOftal), Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza de Ramón y Cajal, s/n, 28040 Madrid, SpainRetinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, 31008 Pamplona, SpainPharmaceutical Innovation in Ophthalmology (InnOftal), Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza de Ramón y Cajal, s/n, 28040 Madrid, SpainWe assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.https://www.mdpi.com/1424-8247/14/1/50retinal diseasesGDNFBDNFRPE migrationco-deliveryPLGA microspheres |
| spellingShingle | Alicia Arranz-Romera Maria Hernandez Patricia Checa-Casalengua Alfredo Garcia-Layana Irene T. Molina-Martinez Sergio Recalde Michael J. Young Budd A. Tucker Rocío Herrero-Vanrell Patricia Fernandez-Robredo Irene Bravo-Osuna A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies Pharmaceuticals retinal diseases GDNF BDNF RPE migration co-delivery PLGA microspheres |
| title | A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies |
| title_full | A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies |
| title_fullStr | A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies |
| title_full_unstemmed | A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies |
| title_short | A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies |
| title_sort | safe gdnf and gdnf bdnf controlled delivery system improves migration in human retinal pigment epithelial cells and survival in retinal ganglion cells potential usefulness in degenerative retinal pathologies |
| topic | retinal diseases GDNF BDNF RPE migration co-delivery PLGA microspheres |
| url | https://www.mdpi.com/1424-8247/14/1/50 |
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