{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T09:32:48Z","timestamp":1779010368681,"version":"3.51.4"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish National Science Centre","award":["2016\/21\/B\/NZ5\/01411"],"award-info":[{"award-number":["2016\/21\/B\/NZ5\/01411"]}]},{"name":"Medical University of Lodz, Poland","award":["502-03\/5-108-05\/502-54-224-18"],"award-info":[{"award-number":["502-03\/5-108-05\/502-54-224-18"]}]},{"name":"Medical University of Lodz, Poland","award":["564\/5-000-00\/564-20-043"],"award-info":[{"award-number":["564\/5-000-00\/564-20-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.<\/jats:p>","DOI":"10.3390\/ijms22094494","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T02:31:43Z","timestamp":1619490703000},"page":"4494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9206-1203","authenticated-orcid":false,"given":"Wioletta","family":"Rozp\u0119dek-Kami\u0144ska","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Galita","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-580X","authenticated-orcid":false,"given":"Natalia","family":"Siwecka","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Alan","family":"Diehl","sequence":"additional","affiliation":[{"name":"Hollings Cancer Center, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Kucharska","sequence":"additional","affiliation":[{"name":"Department of Gerontology, Geriatrics and Social Work, Jesuit University Ignatianum, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dariusz","family":"Pytel","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland"},{"name":"Hollings Cancer Center, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ireneusz","family":"Majsterek","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1089\/jop.2017.0041","article-title":"Targets of Neuroprotection in Glaucoma","volume":"34","author":"He","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0161-6420(02)01568-3","article-title":"Temba glaucoma study: A population-based cross-sectional survey in urban South Africa","volume":"110","author":"Rotchford","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1590\/S0004-27492011000200001","article-title":"Managing glaucoma in developing countries","volume":"74","author":"Leite","year":"2011","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_6","first-page":"844","article-title":"Global data on visual impairment in the year 2002","volume":"82","author":"Resnikoff","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3341\/kjo.2012.26.2.97","article-title":"Anterior chamber configuration changes after cataract surgery in eyes with glaucoma","volume":"26","author":"Kim","year":"2012","journal-title":"Korean J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jcjo.2016.12.010","article-title":"Undetected angle closure in patients with a diagnosis of open-angle glaucoma","volume":"52","author":"Varma","year":"2017","journal-title":"Can. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/eye.2011.309","article-title":"Current concepts on primary open-angle glaucoma genetics: A contribution to disease pathophysiology and future treatment","volume":"26","author":"Gemenetzi","year":"2012","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rozpedek-Kaminska, W., Wojtczak, R., Szaflik, J.P., Szaflik, J., and Majsterek, I. (2020). The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114171"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109405","DOI":"10.1016\/j.mehy.2019.109405","article-title":"Is \u201cnormal tension glaucoma\u201d glaucoma?","volume":"133","author":"Fan","year":"2019","journal-title":"Med. Hypotheses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1001\/jama.2013.5099","article-title":"Do findings on routine examination identify patients at risk for primary open-angle glaucoma? The rational clinical examination systematic review","volume":"309","author":"Hollands","year":"2013","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.ophtha.2006.06.022","article-title":"Ocular Hypertension Treatment Study, G. Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study","volume":"113","author":"Budenz","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_15","first-page":"145","article-title":"Evaluation of the myocilin (MYOC) glaucoma gene in monkey and human steroid-induced ocular hypertension","volume":"42","author":"Fingert","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","first-page":"578","article-title":"Involvement of ER stress in retinal cell death","volume":"13","author":"Shimazawa","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.brainres.2009.10.025","article-title":"Retinal ganglion cell death induced by endoplasmic reticulum stress in a chronic glaucoma model","volume":"1308","author":"Doh","year":"2010","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1167\/iovs.18-25477","article-title":"Endoplasmic Reticulum Stress Response of Trabecular Meshwork Stem Cells and Trabecular Meshwork Cells and Protective Effects of Activated PERK Pathway","volume":"60","author":"Wang","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1523\/JNEUROSCI.3709-15.2016","article-title":"Rescue of Glaucomatous Neurodegeneration by Differentially Modulating Neuronal Endoplasmic Reticulum Stress Molecules","volume":"36","author":"Yang","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pharmthera.2011.01.013","article-title":"Carbon monoxide and the eye: Implications for glaucoma therapy","volume":"130","author":"Bucolo","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/B978-0-12-407704-1.00005-1","article-title":"Endoplasmic reticulum and the unfolded protein response: Dynamics and metabolic integration","volume":"301","author":"Bravo","year":"2013","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The endoplasmic reticulum: Structure, function and response to cellular signaling","volume":"73","author":"Schwarz","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"a013169","DOI":"10.1101\/cshperspect.a013169","article-title":"Endoplasmic reticulum stress sensing in the unfolded protein response","volume":"5","author":"Gardner","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Siwecka, N., Rozpedek, W., Pytel, D., Wawrzynkiewicz, A., Dziki, A., Dziki, L., Diehl, J.A., and Majsterek, I. (2019). Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184354"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fmolb.2019.00011","article-title":"Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1","volume":"6","author":"Adams","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1089\/ars.2009.2485","article-title":"Role of the unfolded protein response regulator GRP78\/BiP in development, cancer, and neurological disorders","volume":"11","author":"Wang","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44723","DOI":"10.1038\/srep44723","article-title":"The Endoplasmic Reticulum Chaperone GRP78\/BiP Modulates Prion Propagation in vitro and in vivo","volume":"7","author":"Park","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1016\/j.febslet.2007.04.045","article-title":"ER chaperones in mammalian development and human diseases","volume":"581","author":"Ni","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00211","DOI":"10.1002\/prp2.211","article-title":"Role of endoplasmic reticulum stress in drug-induced toxicity","volume":"4","author":"Foufelle","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.semcdb.2007.09.003","article-title":"The endoplasmic reticulum and the unfolded protein response","volume":"18","author":"Malhotra","year":"2007","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1822","DOI":"10.1038\/cddis.2015.183","article-title":"Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate","volume":"6","author":"Liu","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41467-017-00171-w","article-title":"A non-canonical pathway regulates ER stress signaling and blocks ER stress-induced apoptosis and heart failure","volume":"8","author":"Yao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2174\/1567205016666190228121157","article-title":"Inhibition of the PERK-dependent Unfolded Protein Response signaling pathway involved in the pathogenesis of Alzheimer\u2019s disease","volume":"16","author":"Rozpedek","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rozpedek-Kaminska, W., Siwecka, N., Wawrzynkiewicz, A., Wojtczak, R., Pytel, D., Diehl, J.A., and Majsterek, I. (2020). The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062108"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/sj.embor.7400779","article-title":"Mediators of endoplasmic reticulum stress-induced apoptosis","volume":"7","author":"Szegezdi","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bbcan.2016.12.002","article-title":"Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer","volume":"1867","author":"Bhat","year":"2017","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00204-014-1240-8","article-title":"The transcription factor CHOP, a central component of the transcriptional regulatory network induced upon CCl4 intoxication in mouse liver, is not a critical mediator of hepatotoxicity","volume":"88","author":"Campos","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1371\/journal.pgen.0010004","article-title":"Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage","volume":"1","author":"Libby","year":"2005","journal-title":"PLoS Genet."},{"key":"ref_39","first-page":"155","article-title":"The expression of Bcl-2, Bcl-xl, Bak and Bax proteins in axons of the optic nerve in closed-angle glaucoma","volume":"106","author":"Zalewska","year":"2004","journal-title":"Klin. Ocz."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.2147\/OPTH.S264839","article-title":"Minimally Invasive Surgery in Mild-to-Moderate Glaucoma Patients in Italy: Is It Time to Change?","volume":"14","author":"Costagliola","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108831","DOI":"10.1016\/j.radphyschem.2020.108831","article-title":"Reactions of radicals with PERK kinase inhibitor and its analogue under oxidative and reductive stress conditions. Pulse radiolysis study","volume":"172","author":"Radomska","year":"2020","journal-title":"Radiat. Phys. Chem."},{"key":"ref_42","first-page":"25","article-title":"Inhibitor of pro-apoptotic PERK-dependent signalling pathway as a novel treatment strategy in Alzheimer\u2019s disease treatment","volume":"35","author":"Rozpedek","year":"2019","journal-title":"Pharmacother. Psychiatry Neurol."},{"key":"ref_43","first-page":"9","article-title":"Niskocz\u0105steczkowe inhibitory szlaku Adaptacyjnej odpowiedzi na stres zale\u017cnego od kinazy PERK jako nowatorska strategia terapeutyczna w leczeniu choroby Alzheimera","volume":"46","author":"Rozpedek","year":"2019","journal-title":"Pol. Merkur. Lek."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mrrev.2005.11.001","article-title":"The role of oxidative stress in glaucoma","volume":"612","author":"Izzotti","year":"2006","journal-title":"Mutat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1001\/archopht.123.4.458","article-title":"Oxidative DNA damage in the human trabecular meshwork: Clinical correlation in patients with primary open-angle glaucoma","volume":"123","author":"Sacca","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3109\/02713683.2011.584370","article-title":"Antioxidant status and oxidative stress in primary open angle glaucoma and pseudoexfoliative glaucoma","volume":"36","author":"Erdurmus","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/IJG.0b013e31815c3a7f","article-title":"Oxidative stress in primary open-angle glaucoma","volume":"17","year":"2008","journal-title":"J. Glaucoma"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.freeradbiomed.2004.06.001","article-title":"Retinal oxidative stress induced by high intraocular pressure","volume":"37","author":"Moreno","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Abu-Hassan, D.W., Acott, T.S., and Kelley, M.J. (2014). The Trabecular Meshwork: A Basic Review of Form and Function. J. Ocul. Biol., 2.","DOI":"10.13188\/2334-2838.1000017"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.exer.2008.01.013","article-title":"Extracellular matrix in the trabecular meshwork","volume":"86","author":"Acott","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.exer.2005.10.011","article-title":"What controls aqueous humour outflow resistance?","volume":"82","author":"Johnson","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_52","first-page":"1513","article-title":"Apoptosis in the trabecular meshwork of glaucomatous patients","volume":"14","author":"Baleriola","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0161-6420(84)34248-8","article-title":"Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals","volume":"91","author":"Alvarado","year":"1984","journal-title":"Ophthalmology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0014-4835(86)90004-7","article-title":"Quantitative analysis of \u2018plaque material\u2019 in the inner- and outer wall of Schlemm\u2019s canal in normal- and glaucomatous eyes","volume":"42","author":"Shimizu","year":"1986","journal-title":"Exp. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"202905","DOI":"10.1155\/2013\/202905","article-title":"Integrins in trabecular meshwork and optic nerve head: Possible association with the pathogenesis of glaucoma","volume":"2013","author":"Zhong","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/bs.pmbts.2015.04.008","article-title":"Glaucoma Genes and Mechanisms","volume":"134","author":"Wiggs","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.bbrc.2003.10.162","article-title":"Accumulation of mutant myocilins in ER leads to ER stress and potential cytotoxicity in human trabecular meshwork cells","volume":"312","author":"Joe","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1172\/JCI69774","article-title":"Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma","volume":"124","author":"Zode","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.14-16220","article-title":"Increased Endoplasmic Reticulum Stress in Human Glaucomatous Trabecular Meshwork Cells and Tissues","volume":"56","author":"Peters","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1172\/JCI58183","article-title":"Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma","volume":"121","author":"Zode","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1093\/hmg\/ddu730","article-title":"Structural basis for misfolding in myocilin-associated glaucoma","volume":"24","author":"Donegan","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1167\/iovs.11-8837","article-title":"Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a myocilin mouse model of primary open-angle glaucoma","volume":"53","author":"Zode","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1093\/hmg\/8.12.2221","article-title":"A cellular assay distinguishes normal and mutant TIGR\/myocilin protein","volume":"8","author":"Zhou","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1167\/iovs.09-4118","article-title":"Functional role of proteolytic processing of recombinant myocilin in self-aggregation","volume":"51","author":"Escribano","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.exer.2015.08.017","article-title":"Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma","volume":"144","author":"Stothert","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/978-1-4939-7407-8_12","article-title":"Methods for Analyzing Endoplasmic Reticulum Stress in the Trabecular Meshwork of Glaucoma Models","volume":"1695","author":"Maddineni","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2353\/ajpath.2007.060806","article-title":"Aggregated myocilin induces russell bodies and causes apoptosis: Implications for the pathogenesis of myocilin-caused primary open-angle glaucoma","volume":"170","author":"Yam","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1167\/iovs.16-19610","article-title":"Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork","volume":"57","author":"Kasetti","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"40661","DOI":"10.1074\/jbc.M112.384800","article-title":"Glucose-regulated protein 94 triage of mutant myocilin through endoplasmic reticulum-associated degradation subverts a more efficient autophagic clearance mechanism","volume":"287","author":"Suntharalingam","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Carbone, M.A., Ayroles, J.F., Yamamoto, A., Morozova, T.V., West, S.A., Magwire, M.M., Mackay, T.F., and Anholt, R.R. (2009). Overexpression of myocilin in the Drosophila eye activates the unfolded protein response: Implications for glaucoma. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004216"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"206ra138","DOI":"10.1126\/scitranslmed.3006767","article-title":"Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice","volume":"5","author":"Moreno","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00401-015-1487-z","article-title":"PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia","volume":"130","author":"Radford","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.nbd.2018.01.004","article-title":"Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson\u2019s disease","volume":"112","author":"Mercado","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8628","DOI":"10.18632\/aging.202677","article-title":"Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG","volume":"13","author":"Ying","year":"2021","journal-title":"Aging"},{"key":"ref_75","first-page":"1122","article-title":"Down-regulation of GRP78 in human glaucomatous trabecular meshwork cells","volume":"16","author":"Chai","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14951","DOI":"10.1038\/s41598-017-14938-0","article-title":"Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork","volume":"7","author":"Kasetti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1016\/j.bbamcr.2016.06.008","article-title":"Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53","volume":"1863","author":"Kalouche","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5594","DOI":"10.1038\/s41467-020-19352-1","article-title":"ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load","volume":"11","author":"Kasetti","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_79","first-page":"563","article-title":"Accumulation of Asn450Tyr mutant myocilin in ER promotes apoptosis of human trabecular meshwork cells","volume":"26","author":"Yan","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Napoli, P.E., Nioi, M., Mangoni, L., Gentile, P., Braghiroli, M., d\u2019Aloja, E., and Fossarello, M. (2020). Fourier-Domain OCT Imaging of the Ocular Surface and Tear Film Dynamics: A Review of the State of the Art and an Integrative Model of the Tear Behavior During the Inter-Blink Period and Visual Fixation. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030668"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jcjo.2013.10.003","article-title":"Qualitative and quantitative analysis of filtering blebs with optical coherence tomography","volume":"49","author":"Napoli","year":"2014","journal-title":"Can. J. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1177\/1087057114525853","article-title":"Enzymatic Characterization of ER Stress-Dependent Kinase, PERK, and Development of a High-Throughput Assay for Identification of PERK Inhibitors","volume":"19","author":"Pytel","year":"2014","journal-title":"J. Biomol. Screen."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:52:48Z","timestamp":1760161968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,26]]},"references-count":82,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094494"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,26]]}}}