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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Drug Delivery |
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| Online Access: | http://dx.doi.org/10.1080/10717544.2021.1998245 |
| _version_ | 1818979853033013248 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T17:06:07Z |
| format | Article |
| id | doaj.art-e922018f63d543ec9289e68fb4866160 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-20T17:06:07Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-e922018f63d543ec9289e68fb48661602022-12-21T19:32:16ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642021-01-012812427244610.1080/10717544.2021.19982451998245Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheresMJ Rodrigo0D Garcia-Herranz1A Aragón-Navas2M Subias3T Martinez-Rincón4S Mendez-Martínez5MJ Cardiel6J García-Feijoo7J Ruberte8R Herrero-Vanrell9L Pablo10E Garcia-Martin11I Bravo-Osuna12Department of Ophthalmology, Miguel Servet University HospitalComplutense University of Madrid. Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of MadridComplutense University of Madrid. Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of MadridDepartment of Ophthalmology, Miguel Servet University HospitalDepartment of Ophthalmology, Miguel Servet University HospitalDepartment of Ophthalmology, Miguel Servet University HospitalMiguel Servet Ophthalmology Research Group (GIMSO), University of Zaragoza, Aragon Health Research Institute (IIS Aragon)Complutense University of Madrid. Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415. National Ocular Pathology Network (OFTARED), Carlos III Health InstituteAnimal Biotechnology and Gene Therapy Centre (CBATEG), Universitat Autònoma de BarcelonaNational Ocular Pathology Network (OFTARED), Carlos III Health InstituteDepartment of Ophthalmology, Miguel Servet University HospitalDepartment of Ophthalmology, Miguel Servet University HospitalNational Ocular Pathology Network (OFTARED), Carlos III Health InstitutePurpose 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.http://dx.doi.org/10.1080/10717544.2021.1998245glaucomaanimal modelplga microspheresneurodegenerationdexamethasone |
| spellingShingle | 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 Drug Delivery glaucoma animal model plga microspheres neurodegeneration dexamethasone |
| title | 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_short | 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 |
| topic | glaucoma animal model plga microspheres neurodegeneration dexamethasone |
| url | http://dx.doi.org/10.1080/10717544.2021.1998245 |
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