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. |
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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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