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Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models
Neuroinflammation significantly contributes to the pathophysiology of several neurodegenerative diseases. This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the p...
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| Published in: | Biomolecules (Basel, Switzerland) Switzerland), 2022-02, Vol.12 (2), p.281 |
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| container_issue | 2 |
| container_start_page | 281 |
| container_title | Biomolecules (Basel, Switzerland) |
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| creator | Zeng, Huilan Dumitrescu, Alina V Wadkins, David Elwood, Benjamin W Gramlich, Oliver W Kuehn, Markus H |
| description | Neuroinflammation significantly contributes to the pathophysiology of several neurodegenerative diseases. This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARγ) whose pleiotrophic activities include modulation of cellular energy metabolism and reduction in inflammation. In this study we employed the DBA2/J mouse model of glaucoma with chronically elevated intraocular pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) survival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electroretinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does significantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment preserves and partially reverses vision loss in spite of continuously elevated intraocular pressure. These data suggest that pioglitazone may provide treatment benefits for those glaucoma patients experiencing continued vision loss. |
| doi_str_mv | 10.3390/biom12020281 |
| format | article |
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This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARγ) whose pleiotrophic activities include modulation of cellular energy metabolism and reduction in inflammation. In this study we employed the DBA2/J mouse model of glaucoma with chronically elevated intraocular pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) survival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electroretinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does significantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment preserves and partially reverses vision loss in spite of continuously elevated intraocular pressure. These data suggest that pioglitazone may provide treatment benefits for those glaucoma patients experiencing continued vision loss.</description><identifier>ISSN: 2218-273X</identifier><identifier>EISSN: 2218-273X</identifier><identifier>DOI: 10.3390/biom12020281</identifier><identifier>PMID: 35204782</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alzheimer's disease ; Animal models ; Animals ; Cell survival ; Energy metabolism ; Glaucoma ; Glaucoma - metabolism ; glucose metabolism ; Humans ; Inflammation ; Intraocular Pressure ; Laboratories ; Medical research ; Mice ; Mice, Inbred C57BL ; Neurodegeneration ; Neurodegenerative diseases ; Optic nerve ; Optokinetic response ; Patients ; Peroxisome proliferator-activated receptors ; Pioglitazone ; Pioglitazone - pharmacology ; Pioglitazone - therapeutic use ; PPARγ ; Pressure ; Retina ; Retinal ganglion cells ; Retinal Ganglion Cells - metabolism ; Vision ; Visual perception</subject><ispartof>Biomolecules (Basel, Switzerland), 2022-02, Vol.12 (2), p.281</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARγ) whose pleiotrophic activities include modulation of cellular energy metabolism and reduction in inflammation. In this study we employed the DBA2/J mouse model of glaucoma with chronically elevated intraocular pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) survival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electroretinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does significantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment preserves and partially reverses vision loss in spite of continuously elevated intraocular pressure. These data suggest that pioglitazone may provide treatment benefits for those glaucoma patients experiencing continued vision loss.</description><subject>Alzheimer's disease</subject><subject>Animal models</subject><subject>Animals</subject><subject>Cell survival</subject><subject>Energy metabolism</subject><subject>Glaucoma</subject><subject>Glaucoma - metabolism</subject><subject>glucose metabolism</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Intraocular Pressure</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Optic nerve</subject><subject>Optokinetic response</subject><subject>Patients</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Pioglitazone</subject><subject>Pioglitazone - pharmacology</subject><subject>Pioglitazone - therapeutic use</subject><subject>PPARγ</subject><subject>Pressure</subject><subject>Retina</subject><subject>Retinal ganglion cells</subject><subject>Retinal Ganglion Cells - metabolism</subject><subject>Vision</subject><subject>Visual perception</subject><issn>2218-273X</issn><issn>2218-273X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkt1rFDEUxQdRbKl981kCvvjg1nxMvl4EKVoLKy1apW8hk7nZZslMajJTqX-92W4t2yaBG5LDj5OT2zSvCT5iTOMPXUgDobhORZ41-5QStaCSXT7f2e81h6WscR2qLspeNnuMU9xKRfebyx-3ZYIhOHSRwU4DjBP6E6YrdB7SKobJ_k0joO9wA7lAQb9CCWlEy1QKCiM6z-BiGIOzEZ1EO7s0WPQt9RDLq-aFt7HA4X09aH5--Xxx_HWxPDs5Pf60XLhqYFpIzkTvOuoVgGWu61krekuIY1pqzzsnicWcc9lqrojTXApBuPbMe--4b9lBc7rl9smuzXUOg823Jtlg7g5SXhmbp-AiGNDOVm5LqHJtR7F23gsiO5BU9B6Lyvq4ZV3P3QC9q2FkGx9BH9-M4cqs0o1RWhBBeQW8uwfk9HuGMpkhFAcx2hHSXAwVjClOidz4fvtEuk5zHmtUGxXlmEpKq-r9VuVyjTyDfzBDsNl0gNntgCp_s_uAB_H__2b_AA0orP0</recordid><startdate>20220209</startdate><enddate>20220209</enddate><creator>Zeng, Huilan</creator><creator>Dumitrescu, Alina V</creator><creator>Wadkins, David</creator><creator>Elwood, Benjamin W</creator><creator>Gramlich, Oliver W</creator><creator>Kuehn, Markus H</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5289-0645</orcidid><orcidid>https://orcid.org/0000-0003-3940-198X</orcidid></search><sort><creationdate>20220209</creationdate><title>Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models</title><author>Zeng, Huilan ; 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This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARγ) whose pleiotrophic activities include modulation of cellular energy metabolism and reduction in inflammation. In this study we employed the DBA2/J mouse model of glaucoma with chronically elevated intraocular pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) survival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electroretinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does significantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment preserves and partially reverses vision loss in spite of continuously elevated intraocular pressure. 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| ispartof | Biomolecules (Basel, Switzerland), 2022-02, Vol.12 (2), p.281 |
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| subjects | Alzheimer's disease Animal models Animals Cell survival Energy metabolism Glaucoma Glaucoma - metabolism glucose metabolism Humans Inflammation Intraocular Pressure Laboratories Medical research Mice Mice, Inbred C57BL Neurodegeneration Neurodegenerative diseases Optic nerve Optokinetic response Patients Peroxisome proliferator-activated receptors Pioglitazone Pioglitazone - pharmacology Pioglitazone - therapeutic use PPARγ Pressure Retina Retinal ganglion cells Retinal Ganglion Cells - metabolism Vision Visual perception |
| title | Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models |
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