c7ce07a4fa7d6307ddb1734597c99f6d pmc_33567776.pdf 0f48cec23192b49b8d72c20702778de842665fd2 pmc_33567776.pdf fb2f495d295b1da22d467d0bacbf6757f7c5305d43e837e270d5219ffd4962e0 pmc_33567776.pdf Title: Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration Subject: Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 L suspension; 10% w/v): 14 with 38–20 m Ms (Ms38/20 model) and 25 with 20–10 m particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo. Keywords: PLGA microspheres; intraocular pressure; glaucoma animal model; intracameral injection; optic nerve; neurodegeneration Author: David Garcia-Herranz, Maria Jesus Rodrigo, Manuel Subias, Teresa Martinez-Rincon, Silvia Mendez-Martinez, Irene Bravo-Osuna, Aina Bonet, Jesus Ruberte, Julian Garcia-Feijoo, Luis Pablo, Elena Garcia-Martin and Rocío Herrero-Vanrell Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 23 17:03:59 2021 CET ModDate: Tue Feb 23 17:09:22 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 7807157 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ARIQJE+VnURWPalladioL Type 1 Custom yes yes no 15 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 19 0 ZWFIKU+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 LUNHME+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 JWJGBQ+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 IAFAOG+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 41 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 69 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 73 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 77 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 92 0 PAPJJI+PalatinoLinotype TrueType WinAnsi yes yes no 108 0 PAPJKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 111 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:31:21 CEST RepresentationInformation: pmc_33567776.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:08:51 CEST Size: 7807157 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 401 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: Materials Destination: subsection.2.1 Item: Title: Manufacture of PLGA Microspheres Destination: subsection.2.2 Item: Title: Microsphere Characterization Destination: subsection.2.3 Children: Item: Title: Production Yield Percentage (PY%) Destination: subsubsection.2.3.1 Item: Title: Morphological Evaluation Destination: subsubsection.2.3.2 Item: Title: Mean Particle Size and Particle Size Distribution Destination: subsubsection.2.3.3 Item: Title: Animals Destination: subsection.2.4 Item: Title: Ocular Hypertension (OHT) Induction Destination: subsection.2.5 Item: Title: Ophthalmological Studies Destination: subsection.2.6 Children: Item: Title: In Vivo Destination: subsubsection.2.6.1 Item: Title: Postmortem Destination: subsubsection.2.6.2 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Production Yield, Mean Particle Size and Particle Size Distribution Destination: subsection.3.1 Item: Title: Morphological Evaluation Destination: subsection.3.2 Item: Title: Ophthalmological Clinical Signs Destination: subsection.3.3 Item: Title: Localization of Microspheres in Injected Eyes Destination: subsection.3.4 Item: Title: Intraocular Pressure (IOP) Destination: subsection.3.5 Item: Title: Neuroretinal Examination Destination: subsection.3.6 Children: Item: Title: In Vivo OCT Destination: subsubsection.3.6.1 Item: Title: Postmortem Examination Destination: subsubsection.3.6.2 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration Author: David Garcia-Herranz, Maria Jesus Rodrigo, Manuel Subias, Teresa Martinez-Rincon, Silvia Mendez-Martinez, Irene Bravo-Osuna, Aina Bonet, Jesus Ruberte, Julian Garcia-Feijoo, Luis Pablo, Elena Garcia-Martin and Rocío Herrero-Vanrell Subject: Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 L suspension; 10% w/v): 14 with 38 20 m Ms (Ms38/20 model) and 25 with 20 10 m particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo. Keywords: PLGA microspheres; intraocular pressure; glaucoma animal model; intracameral injection; optic nerve; neurodegeneration Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 23 17:03:59 CET 2021 ModDate: Tue Feb 23 17:09:22 CET 2021 ID: 0xacd9d6ad474bcdf1d72bdc9a2c8184c9, 0xacd9d6ad474bcdf1d72bdc9a2c8184c9 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: JWJGBQ+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: JWJGBQ+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: OVNEXW+EURM10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: OVNEXW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: ZWFIKU+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: ZWFIKU+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: 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