Mimicking chronic glaucoma over 6 months with a single intracameral injection of dexamethasone/fibronectin-loaded PLGA microspheres
Aragón-Navas, Alba (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Rodrigo Sanjuan, María Jesús (Instituto de Salud Carlos III)
Garcia-Herranz, David (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Martínez-Rincón, Teresa (Universidad de Zaragoza. Instituto de Investigación Sanitaria de Aragón)
Subías, Manuel (Universidad de Zaragoza. Instituto de Investigación Sanitaria de Aragón)
Mendez-Martínez, Silvia (Universidad de Zaragoza. Instituto de Investigación Sanitaria de Aragón)
Ruberte, Jesús (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Pampalona Sala, Judit (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Bravo-Osuna, Irene (Instituto de Salud Carlos III)
Pablo, Luis E. (Instituto de Salud Carlos III)
Garcia-Martin, Elena (Instituto de Salud Carlos III)
Herrero-Vanrell, Rocío (Instituto de Salud Carlos III)

Data:	2022
Resum:	To create a chronic glaucoma animal model by a single intracameral injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (Ms) co-loaded with dexamethasone and fibronectin (MsDexaFibro). MsDexaFibro were prepared by a water-in-oil-in-water emulsion method including dexamethasone in the organic phase and fibronectin in the inner aqueous phase. To create the chronic glaucoma model, an interventionist and longitudinal animal study was performed using forty-five Long Evans rats (4-week-old). Rats received a single intracameral injection of MsDexafibro suspension (10%w/v) in the right eye. Ophthalmological parameters such as clinical signs, intraocular pressure (IOP), neuro-retinal functionality by electroretinography (ERG), retinal structural analysis by optical coherence tomography (OCT), and histology were evaluated up to six months. According to the results obtained, the model proposed was able to induce IOP increasing in both eyes over the study, higher in the injected eyes up to 6 weeks (p < 0. 05), while preserving the ocular surface. OCT quantified progressive neuro-retinal degeneration (mainly in the retinal nerve fiber layer) in both eyes but higher in the injected eye. Ganglion cell functionality decreased in injected eyes, thus smaller amplitudes in PhNR were detected by ERG. In conclusion, a new chronic glaucoma animal model was created by a single injection of MsDexaFibro very similar to open-angle glaucoma occurring in humans. This model would impact in different fields such as ophthalmology, allowing long period of study of this pathology; pharmacology, evaluating the neuroprotective activity of active compounds; and pharmaceutical technology, allowing the correct evaluation of the efficacy of long-term sustained ocular drug delivery systems.
Ajuts:	Instituto de Salud Carlos III MAT2017-83858-C2-2 Instituto de Salud Carlos III MAT2017-83858-C2-1 Ministerio de Ciencia e Innovación PRE2018-083951
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Glaucoma animal model ; PLGA microspheres ; Multiloaded ; Intraocular pressure ; Neurodegeneration
Publicat a:	Drug Delivery, Vol. 29 (july 2022) , p. 2357-2374, ISSN 1521-0464

DOI: 10.1080/10717544.2022.2096712
PMID: 35904152

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