Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres

Purpose To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. Methods Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the r...

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Autores principales:	MJ Rodrigo, D Garcia-Herranz, A Aragón-Navas, M Subias, T Martinez-Rincón, S Mendez-Martínez, MJ Cardiel, J García-Feijoo, J Ruberte, R Herrero-Vanrell, L Pablo, E Garcia-Martin, I Bravo-Osuna
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	glaucoma animal model plga microspheres neurodegeneration dexamethasone Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e922018f63d543ec9289e68fb4866160
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spelling	oai:doaj.org-article:e922018f63d543ec9289e68fb48661602021-11-17T14:21:55ZLong-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres1071-75441521-046410.1080/10717544.2021.1998245https://doaj.org/article/e922018f63d543ec9289e68fb48661602021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.1998245https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Purpose To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. Methods Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0–12–24 weeks. Histological studies were also performed. Results IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. Conclusions This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.MJ RodrigoD Garcia-HerranzA Aragón-NavasM SubiasT Martinez-RincónS Mendez-MartínezMJ CardielJ García-FeijooJ RuberteR Herrero-VanrellL PabloE Garcia-MartinI Bravo-OsunaTaylor & Francis Grouparticleglaucomaanimal modelplga microspheresneurodegenerationdexamethasoneTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2427-2446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glaucoma animal model plga microspheres neurodegeneration dexamethasone Therapeutics. Pharmacology RM1-950
spellingShingle	glaucoma animal model plga microspheres neurodegeneration dexamethasone Therapeutics. Pharmacology RM1-950 MJ Rodrigo D Garcia-Herranz A Aragón-Navas M Subias T Martinez-Rincón S Mendez-Martínez MJ Cardiel J García-Feijoo J Ruberte R Herrero-Vanrell L Pablo E Garcia-Martin I Bravo-Osuna Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
description	Purpose To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. Methods Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0–12–24 weeks. Histological studies were also performed. Results IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. Conclusions This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.
format	article
author	MJ Rodrigo D Garcia-Herranz A Aragón-Navas M Subias T Martinez-Rincón S Mendez-Martínez MJ Cardiel J García-Feijoo J Ruberte R Herrero-Vanrell L Pablo E Garcia-Martin I Bravo-Osuna
author_facet	MJ Rodrigo D Garcia-Herranz A Aragón-Navas M Subias T Martinez-Rincón S Mendez-Martínez MJ Cardiel J García-Feijoo J Ruberte R Herrero-Vanrell L Pablo E Garcia-Martin I Bravo-Osuna
author_sort	MJ Rodrigo
title	Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
title_short	Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
title_full	Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
title_fullStr	Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
title_full_unstemmed	Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres
title_sort	long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded plga microspheres
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/e922018f63d543ec9289e68fb4866160
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Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres

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