{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:18:52Z","timestamp":1770974332030,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital","award":["CMRPG3G1571"],"award-info":[{"award-number":["CMRPG3G1571"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG3K2271"],"award-info":[{"award-number":["CMRPG3K2271"]}]},{"name":"Chang Gung Memorial Hospital","award":["MOST 106-2314-B-182A-046"],"award-info":[{"award-number":["MOST 106-2314-B-182A-046"]}]},{"name":"Chang Gung Memorial Hospital","award":["MOST 109-2314-B-182A-023"],"award-info":[{"award-number":["MOST 109-2314-B-182A-023"]}]},{"name":"Ministry of Science and Technology","award":["CMRPG3G1571"],"award-info":[{"award-number":["CMRPG3G1571"]}]},{"name":"Ministry of Science and Technology","award":["CMRPG3K2271"],"award-info":[{"award-number":["CMRPG3K2271"]}]},{"name":"Ministry of Science and Technology","award":["MOST 106-2314-B-182A-046"],"award-info":[{"award-number":["MOST 106-2314-B-182A-046"]}]},{"name":"Ministry of Science and Technology","award":["MOST 109-2314-B-182A-023"],"award-info":[{"award-number":["MOST 109-2314-B-182A-023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL\/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg\/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg\/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL\/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg\/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg\/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-\u03b3 inhibitor) (1 mg\/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg\/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 \u00b1 4.9 cells\/field) than in group 2 (24.0 \u00b1 11.5 cells\/field) and 3 (25.0 \u00b1 7.7 cells\/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 \u00b1 2.6 cells\/field; group 2: 15.6 \u00b1 3.5 cells\/field; and group 3: 14.8 \u00b1 7.5 cells\/field) and retinal thinning (group 1: 6.7 \u00b1 5.7 \u03bcm; group 2: 12.8 \u00b1 6.1 \u03bcm; and group 3: 15.8 \u00b1 5.8 \u03bcm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 \u00b1 140 Brn3A+ cells\/mm2, n = 7) than in group 1 (1920 \u00b1 228 Brn3A+ cells\/mm2; p = 0.03, n = 4), group 3 (1938 \u00b1 213 Brn3A+ cells\/mm2; p = 0.002, n = 4), and group 4 (2138 \u00b1 126 Brn3A+ cells\/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.<\/jats:p>","DOI":"10.3390\/ijms24010411","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:45:54Z","timestamp":1672116354000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protective Effect of Pioglitazone on Retinal Ganglion Cells in an Experimental Mouse Model of Ischemic Optic Neuropathy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-2582","authenticated-orcid":false,"given":"Ming-Hui","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-8391","authenticated-orcid":false,"given":"Kuan-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Chin","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung 20401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-5739","authenticated-orcid":false,"given":"Rong-Kung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan"},{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1167\/iovs.04-1361","article-title":"Vascular damage in a mouse model of diabetic retinopathy: Relation to neuronal and glial changes","volume":"46","author":"Kinouchi","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1167\/iovs.14-16289","article-title":"Characterization of Retinal Vascular and Neural Damage in a Novel Model of Diabetic Retinopathy","volume":"56","author":"Weerasekera","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1001\/archopht.1996.01100140194013","article-title":"A mouse model of diabetic retinopathy","volume":"114","author":"Kern","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"582060","DOI":"10.1155\/2015\/582060","article-title":"Diabetic Retinopathy: Vascular and Inflammatory Disease","volume":"2015","author":"Semeraro","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exer.2013.12.002","article-title":"Acridine orange leukocyte fluorography in mice","volume":"120","author":"Cahoon","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.preteyeres.2008.11.002","article-title":"Ischemic optic neuropathy","volume":"28","author":"Hayreh","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1056\/NEJMra1413352","article-title":"Ischemic Optic Neuropathies","volume":"372","author":"Biousse","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chen, T., Song, D., Shan, G., Wang, K., Wang, Y., Ma, J., and Zhong, Y. (2013). The association between diabetes mellitus and nonarteritic anterior ischemic optic neuropathy: A systematic review and meta-analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076653"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.ophtha.2011.01.054","article-title":"Incidence of nonarteritic anterior ischemic optic neuropathy: Increased risk among diabetic patients","volume":"118","author":"Lee","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1016\/j.ophtha.2008.03.032","article-title":"Nonarteritic anterior ischemic optic neuropathy: Clinical characteristics in diabetic patients versus nondiabetic patients","volume":"115","author":"Hayreh","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1001\/archophthalmol.2011.209","article-title":"Early diabetes mellitus or hypertension is not significantly associated with severity of vision loss in nonarteritic anterior ischemic optic neuropathy","volume":"129","author":"Odette","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ophtha.2016.11.029","article-title":"Comparison of Visual Outcomes of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients with and without Diabetes Mellitus","volume":"124","author":"Sharma","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1167\/iovs.16-20308","article-title":"Experimental Anterior Ischemic Optic Neuropathy in Diabetic Mice Exhibited Severe Retinal Swelling Associated with VEGF Elevation","volume":"58","author":"Sun","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12222","DOI":"10.1073\/pnas.97.22.12222","article-title":"Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation","volume":"97","author":"Du","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"705783","DOI":"10.1155\/2014\/705783","article-title":"The role of microglia in diabetic retinopathy","volume":"2014","author":"Grigsby","year":"2014","journal-title":"J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.exer.2007.01.011","article-title":"AGEs mediated expression and secretion of TNF alpha in rat retinal microglia","volume":"84","author":"Wang","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275435","DOI":"10.1155\/2015\/275435","article-title":"Role of Peroxisome Proliferator-Activated Receptor gamma in Ocular Diseases","volume":"2015","author":"Zhang","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/j.intimp.2006.07.024","article-title":"Pioglitazone limits cyclosporine nephrotoxicity in rats","volume":"6","author":"Pereira","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"295784","DOI":"10.1155\/2008\/295784","article-title":"PPAR-gamma, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches","volume":"2008","author":"Matteucci","year":"2008","journal-title":"PPAR Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1167\/iovs.08-2005","article-title":"Suppression of retinal peroxisome proliferator-activated receptor gamma in experimental diabetes and oxygen-induced retinopathy: Role of NADPH oxidase","volume":"50","author":"Tawfik","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11892-013-0378-8","article-title":"The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus","volume":"13","author":"Yau","year":"2013","journal-title":"Curr. Diabetes Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1167\/iovs.13-11614","article-title":"Protective effect of pioglitazone on retinal ischemia\/reperfusion injury in rats","volume":"54","author":"Zhang","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhu, J., Zhang, J., Ji, M., Gu, H., Xu, Y., Chen, C., and Hu, N. (2013). The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARgamma in retinal neuroprotection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068935"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26395","DOI":"10.1074\/jbc.M114.583880","article-title":"Pioglitazone normalizes insulin signaling in the diabetic rat retina through reduction in tumor necrosis factor \u03b1 and suppressor of cytokine signaling 3","volume":"289","author":"Jiang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.biopha.2017.08.098","article-title":"A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin","volume":"95","author":"Gheibi","year":"2017","journal-title":"Biomed. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1177\/0023677213489548","article-title":"Streptozotocin is equally diabetogenic whether administered to fed or fasted mice","volume":"47","author":"Chaudhry","year":"2013","journal-title":"Lab. Anim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/eye.2014.220","article-title":"Subretinal fluid is common in experimental non-arteritic anterior ischemic optic neuropathy","volume":"28","author":"Yu","year":"2014","journal-title":"Eye"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1167\/iovs.14-15145","article-title":"Optical coherence tomography study of retinal changes in normal aging and after ischemia","volume":"56","author":"Shariati","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5981","DOI":"10.1167\/iovs.13-12419","article-title":"Optical coherence tomography study of experimental anterior ischemic optic neuropathy and histologic confirmation","volume":"54","author":"Ho","year":"2013","journal-title":"Investig. Ophthalmol. Vis. 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