Intravitreous injection of PLGA microspheres encapsulating GDNF promotes the survival of photoreceptors in the rd1/rd1 mouse

Autor: Andrieu-Soler, C., Aubert-Pouessel, A., Doat, M., Serge Picaud, Halhal, M., Simonutti, M., Venier-Julienne, M. C., Benoit, J. P., Behar-Cohen, F.
Přispěvatelé: Aubert, Anne, Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Innovation Thérapeutique, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Fondation Rothschild
Předmět:
genetic structures
Polymers
MESH: Mice
Mutant Strains
Cell Count
MESH: Electroretinography
MESH: Recombinant Proteins
Mice
Polylactic Acid-Polyglycolic Acid Copolymer
MESH: Glial Fibrillary Acidic Protein
MESH: Animals
Fluorescent Antibody Technique
Indirect
Drug Carriers
Mice
Inbred C3H
MESH: Rhodopsin
Retinal Degeneration
Microspheres
Recombinant Proteins
MESH: Polymers
MESH: Drug Carriers
MESH: Cell Survival
MESH: Antigens
Differentiation
MESH: Glial Cell Line-Derived Neurotrophic Factor
Photoreceptor Cells
Vertebrate
Rhodopsin
Cell Survival
MESH: Retinal Degeneration
MESH: Microspheres
[SDV.SP.PG] Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Injections
MESH: Polyglycolic Acid
MESH: Cell Proliferation
Glial Fibrillary Acidic Protein
Electroretinography
Animals
MESH: Injections
MESH: Fluorescent Antibody Technique
Indirect
Glial Cell Line-Derived Neurotrophic Factor
Lactic Acid
MESH: Mice
Inbred C3H
MESH: Mice
Cell Proliferation
MESH: Cell Count
MESH: Vitreous Body
Antigens
Differentiation
Mice
Mutant Strains
eye diseases
Vitreous Body
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
MESH: Photoreceptor Cells
Vertebrate
MESH: Lactic Acid
sense organs
Polyglycolic Acid
Zdroj: Europe PubMed Central
Molecular Vision
Molecular Vision, 2005, 11, pp.1002-11
Molecular Vision, Molecular Vision, 2005, 11, pp.1002-11
ResearcherID
ISSN: 1090-0535
Popis: International audience; PURPOSE: To evaluate the potential delay of the retinal degeneration in rd1/rd1 mice using recombinant human glial cell line-derived neurotrophic factor (rhGDNF) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres. METHODS: rhGDNF-loaded PLGA microspheres were prepared using a water in oil in water (w/o/w) emulsion solvent extraction-evaporation process. In vitro, the rhGDNF release profile was assessed using radiolabeled factor. In vivo, rhGDNF microspheres, blank microspheres, or microspheres loaded with inactivated rhGDNF were injected into the vitreous of rd1/rd1 mice at postnatal day 11 (PN11). The extent of retinal degeneration was examined at PN28 using rhodopsin immunohistochemistry on whole flat-mount retinas, outer nuclear layer (ONL) cell counting on histology sections, and electroretinogram tracings. Immunohistochemical reactions for glial fibrillary acidic protein (GFAP), F4/80, and rhodopsin were performed on cryosections. RESULTS: Significant delay of rod photoreceptors degeneration was observed in mice receiving the rhGDNF-loaded microspheres compared to either untreated mice or to mice receiving blank or inactivated rhGDNF microspheres. The degeneration delay in the eyes receiving the rhGDNF microspheres was illustrated by the increased rhodopsin positive signals, the preservation of significantly higher number of cell nuclei within the ONL, and significant b-wave increase. A reduction of the subretinal glial proliferation was also observed in these treated eyes. No significant intraocular inflammatory reaction was observed after the intravitreous injection of the various microspheres. CONCLUSIONS: A single intravitreous injection of rhGDNF-loaded microspheres slows the retinal degeneration processes in rd1/rd1 mice. The use of injectable, biodegradable polymeric systems in the vitreous enables the efficient delivery of therapeutic proteins for the treatment of retinal diseases.
Databáze: OpenAIRE
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