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

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

doi:10.3390/ph14010050

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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

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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

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, …

Pharmaceuticals (Basel, Switzerland), Vol.14(1), pp.1-24

01/01/2021

DOI: 10.3390/ph14010050

PMID: 33440745

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Abstract

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.

BDNF

co-delivery

GDNF

PLGA microspheres

retinal diseases

retinal ganglion cells

RPE migration

Details

Title: Subtitle: 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
Creators: Alicia Arranz-Romera - Pharmaceutical 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, Spain
Maria Hernandez - Universidad de Navarra
Patricia Checa-Casalengua - Pharmaceutical 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, Spain
Alfredo Garcia-Layana - Clinica Universidad de Navarra
Irene T Molina-Martinez - Pharmaceutical 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, Spain
Sergio Recalde - Universidad de Navarra
Michael J Young - Harvard University
Budd A Tucker - University of Iowa
Rocío Herrero-Vanrell - Pharmaceutical 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, Spain
Patricia Fernandez-Robredo - Clinica Universidad de Navarra
Irene Bravo-Osuna - Pharmaceutical 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, Spain
Resource Type: Journal article
Publication Details: Pharmaceuticals (Basel, Switzerland), Vol.14(1), pp.1-24
DOI: 10.3390/ph14010050
PMID: 33440745
NLM abbreviation: Pharmaceuticals (Basel)
ISSN: 1424-8247
eISSN: 1424-8247
Publisher: MDPI
Grant note: DOI: 10.13039/501100004587, name: Instituto de Salud Carlos III, award: RETICS-FEDER RD 16/0008
Language: English
Date published: 01/01/2021
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9984187240502771

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