c9a88996994681a034863dbfbff4f7de pmc_34208744.pdf a3a332b9866f336e9194eb2fa5becfdb5c0dfe5d pmc_34208744.pdf 23482316788bb3931ec6b3265bb5756a62dee61f87448137391525103a2eb2dd pmc_34208744.pdf Title: Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up Subject: Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10–20 m) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods. Keywords: glaucoma; animal model; microspheres; neurodegeneration Author: Maria Jesus Rodrigo, David Garcia-Herranz, Manuel Subias, Teresa Martinez-Rincón, Silvia Mendez-Martínez, Irene Bravo-Osuna, Ana Carretero, Jesús Ruberte, Julián Garcia-Feijoo, Luis Emilio Pablo, Rocío Herrero-Vanrell and Elena Garcia-Martin Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jun 18 04:28:06 2021 CEST ModDate: Fri Jun 18 04:43:00 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 26 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 7312446 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JCYIDT+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 15 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 19 0 BZQOAJ+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 MCMFTT+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 DHTBUE+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 62 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 66 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 70 0 IJBLVW+CMSY10 Type 1 Builtin yes yes no 85 0 SPXLNH+PazoMath Type 1 Builtin yes yes no 98 0 XIRVNA+EURB10 Type 1 Builtin yes yes no 123 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 127 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:11:54 CEST RepresentationInformation: pmc_34208744.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:14:23 CEST Size: 7312446 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 453 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Methods, Intervention, or Testing Destination: subsection.2.1 Item: Title: Animal Welfare and Anesthesia Destination: subsection.2.2 Item: Title: Injection Procedure for Induced Ocular Hypertension Destination: subsection.2.3 Item: Title: Clinical Signs and Intraocular Pressure Measurements Destination: subsection.2.4 Item: Title: Neuroretinal Examination Destination: subsection.2.5 Children: Item: Title: In Vivo Optical Coherence Tomography Destination: subsubsection.2.5.1 Item: Title: In Vivo Electroretinography Destination: subsubsection.2.5.2 Item: Title: Histology Destination: subsubsection.2.5.3 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Ophthalmological Signs and IOP Destination: subsection.3.1 Item: Title: In Vivo Neuroretinal Analysis by Optical Coherence Tomography Destination: subsection.3.2 Item: Title: In Vivo Electroretinogram Destination: subsection.3.3 Item: Title: Pathological Findings Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up Author: Maria Jesus Rodrigo, David Garcia-Herranz, Manuel Subias, Teresa Martinez-Rincón, Silvia Mendez-Martínez, Irene Bravo-Osuna, Ana Carretero, Jesús Ruberte, Julián Garcia-Feijoo, Luis Emilio Pablo, Rocío Herrero-Vanrell and Elena Garcia-Martin Subject: Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10 20 m) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods. 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