{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:30:29Z","timestamp":1792798229168,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Group UCM 920415 (InnOftal)","award":["UCM 920415"],"award-info":[{"award-number":["UCM 920415"]}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["MAT2017-83858-C2-1-R"],"award-info":[{"award-number":["MAT2017-83858-C2-1-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["MSCA-RISE-3DNEONET\/734907"],"award-info":[{"award-number":["MSCA-RISE-3DNEONET\/734907"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ISCIII-FEDER RETICS (OFTARED)","award":["(RD16\/0008\/0009 and RD16\/0008\/0004)"],"award-info":[{"award-number":["(RD16\/0008\/0009 and RD16\/0008\/0004)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 \u00b5M) and D-\u03b1-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w\/v) in an isotonic buffer solution close to the vitreous temperature (31\u201334 \u00b0C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 \u00b1 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 \u00b1 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-\u03b1, showing significant results (p \u2264 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime.<\/jats:p>","DOI":"10.3390\/pharmaceutics13020234","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T04:33:46Z","timestamp":1612931626000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"Jos\u00e9 Javier","family":"L\u00f3pez-Cano","sequence":"first","affiliation":[{"name":"Research Group (UCM 920415), Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal), Complutense University, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Sigen A.","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology, School of Medicine, University College Dublin, D04 V1W8 Dublin 4, Ireland"},{"name":"Blafar Ltd., Belfield Innovation Park, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0157-1932","authenticated-orcid":false,"given":"Vanessa","family":"Andr\u00e9s-Guerrero","sequence":"additional","affiliation":[{"name":"Research Group (UCM 920415), Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal), Complutense University, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"},{"name":"Thematic Research Network in Ophthalmology (Oftared), Carlos III National Institute of Health, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Tai","sequence":"additional","affiliation":[{"name":"Blafar Ltd., Belfield Innovation Park, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-7872","authenticated-orcid":false,"given":"Irene","family":"Bravo-Osuna","sequence":"additional","affiliation":[{"name":"Research Group (UCM 920415), Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal), Complutense University, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"},{"name":"Thematic Research Network in Ophthalmology (Oftared), Carlos III National Institute of Health, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-571X","authenticated-orcid":false,"given":"Irene Teresa","family":"Molina-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Research Group (UCM 920415), Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal), Complutense University, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"},{"name":"Thematic Research Network in Ophthalmology (Oftared), Carlos III National Institute of Health, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5053-0611","authenticated-orcid":false,"given":"Wenxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology, School of 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Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1167\/iovs.08-2614","article-title":"Structural and functional maturation of the fetal human choriocapillaris","volume":"50","author":"Baba","year":"2009","journal-title":"Investig. Ophthalmol. Vis Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.2147\/CIA.S142685","article-title":"Early and intermediate age-related macular degeneration: Update and clinical review","volume":"12","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neuron.2012.06.018","article-title":"Mechanisms of age-related macular degeneration","volume":"75","author":"Ambati","year":"2012","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"AMD160","DOI":"10.1167\/iovs.18-24882","article-title":"Soft drusen in age-related macular degeneration: Biology and targeting via the oil spill strategies","volume":"59","author":"Curcio","year":"2018","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.3389\/fphar.2018.01280","article-title":"Oxidative stress in age-related macular degeneration: Nrf2 as therapeutic target","volume":"9","author":"Bellezza","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mjafi.2015.12.001","article-title":"Glaucoma: The \u2018black hole\u2019 of irreversible blindness","volume":"72","author":"Parihar","year":"2016","journal-title":"Med. J. Armed Forces India"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/ICU.0000000000000354","article-title":"Lamina cribrosa in glaucoma","volume":"28","author":"Downs","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.optom.2017.06.002","article-title":"Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy","volume":"11","author":"Mcmonnies","year":"2018","journal-title":"J. Optom."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, W., and Lo, A.C.Y. (2018). Diabetic retinopathy: Pathophysiology and treatments. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061816"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/eye.2017.220","article-title":"Role of pericytes in the retina","volume":"32","author":"Santos","year":"2018","journal-title":"Eye"},{"key":"ref_14","first-page":"869","article-title":"Sector retinitis pigmentosa: Report of ten cases and a review of the literature","volume":"25","author":"Coussa","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1073\/pnas.0813178106","article-title":"Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV","volume":"106","author":"Datta","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8627","DOI":"10.1038\/srep08627","article-title":"Intravitreal combination of dexamethasone sodium phosphate and bevacizumab in the treatment of exudative AMD","volume":"5","author":"Vakalis","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108020","DOI":"10.1016\/j.exer.2020.108020","article-title":"Intravitreal bromfenac liposomal suspension (100 \u03bcg\/0.1 mL). A safety study in rabbit eyes","volume":"194","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1097\/IAE.0000000000000525","article-title":"Treatment of exudative age-related macular degeneration with ranibizumab combined with ketorolac eyedrops or photodynamic therapy","volume":"35","author":"Semeraro","year":"2015","journal-title":"Retina"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1166\/jbn.2013.1646","article-title":"Intravitreal administration of dexamethasone-loaded PLGA-TPGS nanoparticles for the treatment of posterior segment diseases","volume":"9","author":"Yang","year":"2013","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14375","DOI":"10.1038\/s41598-019-50884-9","article-title":"d-a-tocopheryl polyethylene glycol 1000 succinate and a small-molecule survivin suppressant synergistically induce apoptosis in SKBR3 breast cancer cells","volume":"9","author":"Neophytou","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.brainres.2008.06.026","article-title":"Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo","volume":"1226","author":"Nakajima","year":"2008","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12137","DOI":"10.18632\/oncotarget.24343","article-title":"Synergistic neuroprotective effect of rasagiline and idebenone against retinal ischemia-reperfusion injury via the Lin28-let-7-Dicer pathway","volume":"9","author":"Lei","year":"2018","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jconrel.2019.01.012","article-title":"Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma","volume":"297","author":"Davis","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00289-012-0747-5","article-title":"Preparation and analysis of a sustained drug delivery system by PLGA\u2013PEG\u2013PLGA triblock copolymers","volume":"69","author":"Khodaverdi","year":"2012","journal-title":"Polym. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1039\/C6TB02158A","article-title":"Modified PLGA-PEG-PLGA thermosensitive hydrogels with suitable thermosensitivity and properties for use in a drug delivery system","volume":"5","author":"Wang","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1021\/bm101572j","article-title":"Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers","volume":"12","author":"Yu","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijpharm.2007.07.026","article-title":"Injectable block copolymer hydrogels for sustained release of a PEGylated drug","volume":"348","author":"Yu","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.15171\/apb.2016.020","article-title":"Stability-indicating HPLC method for simultaneous determination of chloramphenicol, dexamethasone sodium phosphate and tetrahydrozoline hydrochloride in ophthalmic solution","volume":"6","author":"AlAani","year":"2016","journal-title":"Adv. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ejps.2018.07.059","article-title":"Chemical cross-linking: A feasible approach to prolong doxylamine\/pyridoxine release from spray-dried chitosan microspheres","volume":"123","author":"Katsarov","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105026","DOI":"10.1016\/j.ejps.2019.105026","article-title":"Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes","volume":"138","author":"Wu","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1007\/s00289-019-02948-z","article-title":"Swelling and drug delivery kinetics of click-synthesized hydrogels based on various combinations of PEG and star-shaped PCL: Influence of network parameters on swelling and release behavior","volume":"77","author":"Saidi","year":"2020","journal-title":"Polym. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ejpb.2020.08.022","article-title":"In vivo biocompatibility and efficacy of dexamethasone-loaded PLGA-PEG-PLGA thermogel in an alkali-burn induced corneal neovascularization disease model","volume":"155","author":"Chan","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0168-3659(87)90034-4","article-title":"A simple equation for description of solute release I. Fickian and non-fickian release fromm non-swellable devices in the form of slabs, spheres, cylinders or discs","volume":"5","author":"Ritger","year":"1987","journal-title":"J. Control. Release"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.addr.2012.09.028","article-title":"Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC)","volume":"64","author":"Siepmann","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.14227\/DT160209P41","article-title":"Modeling and comparison of dissolution profiles of diltiazem modified-release formulations","volume":"16","author":"Samaha","year":"2009","journal-title":"Dissolution Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.3109\/03639041003680826","article-title":"PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate","volume":"36","author":"Gao","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jsamd.2017.02.003","article-title":"pH-responsive drug release from dependal-M loaded polyacrylamide hydrogels","volume":"2","author":"Dwivedi","year":"2017","journal-title":"J. Sci. Adv. Mater. Devices"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ejpb.2007.02.025","article-title":"Thermoresponsive hydrogels in biomedical applications","volume":"68","author":"Klouda","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sapino, S., Peira, E., Chirio, D., Chindamo, G., Guglielmo, S., Oliaro-Bosso, S., Barbero, R., Vercelli, C., Re, G., and Brunella, V. (2019). Thermosensitive nanocomposite hydrogels for intravitreal delivery of cefuroxime. Nanomaterials, 9.","DOI":"10.3390\/nano9101461"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40942-017-0075-x","article-title":"pH of anti-VEGF agents in the human vitreous: Low impact of very different formulations","volume":"3","author":"Sobolewska","year":"2017","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s00289-007-0807-4","article-title":"PLGA-PEG-PLGA tri-block copolymers as an in-situ gel forming system for calcitonin delivery","volume":"59","author":"Ghahremankhani","year":"2007","journal-title":"Polym. Bull."},{"key":"ref_42","first-page":"779","article-title":"Biodegradable block copolymers for delivery of proteins and water-insoluble drugs","volume":"3","author":"Bonacucina","year":"2002","journal-title":"J. Control. Release"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1021\/je0498412","article-title":"Solubility of dexamethasone sodium phosphate in different solvents","volume":"49","author":"Hao","year":"2004","journal-title":"J. Chem. Eng. Data"},{"key":"ref_44","unstructured":"Sigma Aldrich (2020, September 22). Product Specification\u2014Ketorolac Tris Salt. Available online: https:\/\/api.sigmaaldrich.com\/deepweb\/assets\/sigmaaldrich\/quality\/spec\/371\/992\/K1136-BULK________SIGMA____.pdf."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.actbio.2015.06.014","article-title":"Vitamin E containing polymer micelles for reducing normal cell cytotoxicity and enhancing chemotherapy efficacy","volume":"24","author":"Lee","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13553","DOI":"10.1038\/srep13553","article-title":"Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model","volume":"5","author":"Wu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_47","unstructured":"(2020, October 30). Pubchem-National Library of Medicine Chemical and Physical Properties of Idebenone, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Idebenone."},{"key":"ref_48","unstructured":"Robin, Y. (2020, August 17). Using Tocophersolan for Drug Delivery. Available online: https:\/\/www.pharmtech.com\/view\/using-tocophersolan-drug-delivery."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1253294","DOI":"10.1155\/2017\/1253294","article-title":"Kanamycin sulphate loaded PLGA-Vitamin-E-TPGS long circulating nanoparticles using combined coating of PEG and water-soluble chitosan","volume":"2017","author":"Mustafa","year":"2017","journal-title":"J. Drug Deliv."},{"key":"ref_50","unstructured":"Cayman Chemical (2020, August 17). Product Information of Ketorolac (Tromethamine Salt). Available online: https:\/\/www.caymanchem.com\/pdfs\/70690.pdf."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41598-018-19428-5","article-title":"Comparison between direct contact and extract exposure methods for PFO cytotoxicity evaluation","volume":"8","author":"Srivastava","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.2147\/OPTH.S13708","article-title":"Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells","volume":"4","author":"Ayaki","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/02713689408995786","article-title":"Dexamethasone induced proliferation of cultured retinal pigment epithelial cells","volume":"13","author":"He","year":"1994","journal-title":"Curr. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1210\/endo-106-4-1198","article-title":"Dexamethasone effects on myoblast proliferation and differentiation","volume":"106","author":"Guerriero","year":"1980","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1183\/09031936.06.00078605","article-title":"Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma","volume":"27","author":"Fouty","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fncel.2019.00139","article-title":"Oxidative stress in retinal degeneration promoted by constant LED light","volume":"13","author":"Benedetto","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9208489","DOI":"10.1155\/2017\/9208489","article-title":"Retinal diseases associated with oxidative stress and the effects of a free radical scavenger (edaravone)","volume":"2017","author":"Masuda","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3940241","DOI":"10.1155\/2017\/3940241","article-title":"Ischemic retinopathies: Oxidative stress and inflammation","volume":"2017","author":"Rivera","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dom\u00e8nech, E.B., and Marfany, G. (2020). The Relevance of oxidative stress in the pathogenesis and therapy of retinal dystrophies. Antioxidants, 9.","DOI":"10.3390\/antiox9040347"},{"key":"ref_60","first-page":"100","article-title":"Glucocorticoid receptor signaling in the eye","volume":"176","author":"Sulaiman","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10863-014-9571-y","article-title":"Idebenone and neuroprotection: Antioxidant, pro-oxidant, or electron carrier?","volume":"47","author":"Jaber","year":"2015","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"196","DOI":"10.4097\/kjae.2010.59.3.196","article-title":"Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta","volume":"59","author":"Lee","year":"2010","journal-title":"Korean J. Anesthesiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s10792-005-2034-z","article-title":"Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina","volume":"25","author":"Aydemir","year":"2004","journal-title":"Int. Ophthalmol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"281981","DOI":"10.1155\/2013\/281981","article-title":"Nonsteroidal anti-inflammatory drugs for retinal disease","volume":"2013","author":"Schoenberger","year":"2013","journal-title":"Int. J. Inflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12640-012-9308-9","article-title":"Dexamethasone enhances oxidative stress-induced cell death in murine neural stem cells","volume":"22","author":"Mutsaers","year":"2012","journal-title":"Neurotox. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"989501","DOI":"10.1155\/2014\/989501","article-title":"Intravitreal steroids for the treatment of retinal diseases","volume":"2014","author":"Sarao","year":"2014","journal-title":"Sci. World J."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/2\/234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:50Z","timestamp":1760160050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/2\/234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,7]]},"references-count":66,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["pharmaceutics13020234"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13020234","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,7]]}}}