RT Journal Article
T1 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
A1 Arranz Romera, Alicia
A1 Hernández, Alicia
A1 Checa-Casalengua, Patricia
A1 García-Layana, Alfredo
A1 Molina Martínez, Irene Teresa
A1 Recalde, Sergio
A1 Young, Michael J.
A1 Tucker, Budd A.
A1 Herrero Vanrell, María Del Rocío
A1 Fernández-Robredo, Patricia
A1 Bravo Osuna, Irene
AB 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.
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/118048
UL https://hdl.handle.net/20.500.14352/118048
LA eng
NO Arranz-Romera, A.; Hernandez, M.; Checa-Casalengua, P.; Garcia-Layana, A.; Molina-Martinez, I.T.; Recalde, S.; Young, M.J.; Tucker, B.A.; Herrero-Vanrell, R.; Fernandez-Robredo, P.; et al. 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 2021, 14, 50. https:// doi.org/10.3390/ph14010050
NO Ministerio de Economía, Industria y Competitividad
NO Instituto de Salud Carlos III
NO European Commission
NO Fundación Multiópticas
NO Universidad de Navarra
DS Docta Complutense
RD 6 abr 2025