{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T01:33:59Z","timestamp":1778981639223,"version":"3.51.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Glaucoma is a heterogeneous eye disease causing atrophy of the optic nerve head (ONH). The optic nerve is formed by the axons of the retinal ganglion cells (RGCs) that transmit visual input to the brain. The progressive RGC loss during glaucoma leads to irreversible vision loss. An elevated intraocular pressure (IOP) is described as main risk factor in glaucoma. In this study, a multielectrode array (MEA)-based <jats:italic>ex vivo<\/jats:italic> glaucoma acute model was established and the effects of hydrostatic pressure (10, 30, 60, and 90 mmHg) on the functionality and survival of adult male and female wild-type mouse (C57BL\/6) retinae were investigated. Spontaneous activity, response rate to electrical and light stimulation, and bursting behavior of RGCs was analyzed prior, during, and after pressure stress. No pressure related effects on spontaneous firing and on the response rate of the RGCs were observed. Even a high pressure level (90 mmHg for 2 h) did not disturb the RGC functionality. However, the cells\u2019 bursting behavior significantly changed under 90 mmHg. The number of spikes in bursts doubled during pressure application and stayed on a high level after pressure stress. Addition of the amino sulfonic acid taurine (1 mM) showed a counteracting effect. OFF ganglion cells did not reveal an increase in bursts under pressure stress. Live\/dead staining after pressure application showed no significant changes in RGC survival. The findings of our <jats:italic>ex vivo<\/jats:italic> model suggest that RGCs are tolerant toward high, short-time pressure stress.<\/jats:p>","DOI":"10.3389\/fnins.2022.831392","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T07:06:51Z","timestamp":1643180811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Hydrostatic Pressure on Electrical Retinal Activity in a Multielectrode Array-Based ex vivo Glaucoma Acute Model"],"prefix":"10.3389","volume":"16","author":[{"given":"Claudia","family":"Ingensiep","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Schaffrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Johnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"B1","first-page":"606","article-title":"Hyperbaric pressure and increased susceptibility to glutamate toxicity in retinal ganglion cells in vitro.","volume":"20","author":"Aihara","year":"2014","journal-title":"Mol. Vis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5697","DOI":"10.1523\/JNEUROSCI.2320-18.2019","article-title":"The Augmentation of Retinogeniculate Communication during Thalamic Burst Mode.","volume":"39","author":"Alitto","year":"2019","journal-title":"J. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1471-4159.1981.tb04473.x","article-title":"In vitro retina as an experimental model of the central nervous system.","volume":"37","author":"Ames","year":"1981","journal-title":"J. Neurochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1741-7007-4-20","article-title":"Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma.","volume":"4","author":"Anderson","year":"2006","journal-title":"BMC Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4137\/OED.S17671","article-title":"Time-dependent Gene Profiling Indicates the Presence of Different Phases for Ischemia\/Reperfusion Injury in Retina.","volume":"6","author":"Andreeva","year":"2014","journal-title":"Ophthalmol. Eye Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e99075","DOI":"10.1371\/journal.pone.0099075","article-title":"Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina.","volume":"9","author":"Biswas","year":"2014","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1167\/iovs.04-0421","article-title":"The gradient of retinal functional changes during acute intraocular pressure elevation.","volume":"46","author":"Bui","year":"2005","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.21769\/BioProtoc.3559","article-title":"Optic nerve crush in mice to study retinal ganglion cell survival and regeneration.","volume":"10","author":"Cameron","year":"2020","journal-title":"Bio. Protoc."},{"key":"B9","first-page":"923","article-title":"Effects of prenatal taurine on mRNA expression of PKA CREB signal pathway and glial cell line derived neurotrophic factor in fetal rat brains of intrauterine growth restriction.","volume":"11","author":"Chen","year":"2009","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B10","first-page":"749","article-title":"Astrocytes in the optic nerve head express putative mechanosensitive channels.","volume":"21","author":"Choi","year":"2015","journal-title":"Mol. Vis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"17444","DOI":"10.1523\/JNEUROSCI.5461-12.2013","article-title":"Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma.","volume":"33","author":"Della Santina","year":"2013","journal-title":"J. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s00726-006-0396-9","article-title":"Taurine increases mitochondrial buffering of calcium: role in neuroprotection.","volume":"34","author":"El Idrissi","year":"2008","journal-title":"Amino. Acids"},{"key":"B13","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1167\/iovs.03-0503","article-title":"Osmoregulation of taurine transporter function and expression in retinal pigment epithelial, ganglion, and muller cells.","volume":"45","author":"El-Sherbeny","year":"2004","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1167\/iovs.12-10581","article-title":"Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental glaucoma.","volume":"54","author":"Frankfort","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e42017","DOI":"10.1371\/journal.pone.0042017","article-title":"Taurine provides neuroprotection against retinal ganglion cell degeneration.","volume":"7","author":"Froger","year":"2012","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/978-1-4614-6130-2_6","article-title":"Taurine is a crucial factor to preserve retinal ganglion cell survival.","volume":"775","author":"Froger","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"B17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0014-4835(95)80056-5","article-title":"Programmed cell death of retinal ganglion cells during experimental glaucoma.","volume":"61","author":"Garcia-Valenzuela","year":"1995","journal-title":"Exp. Eye Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/s0039-6257(99)00054-5","article-title":"Retinal ganglion cell dysfunction induced by hypoxia and glutamate: potential neuroprotective effects of \u03b2-Blockers.","volume":"43","author":"Gross","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"B19","first-page":"81","article-title":"Electroretinography of acute hypoxic and increased intraocular pressure status in the dog.","volume":"36","author":"Howard","year":"1975","journal-title":"Am. J. Vet. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/IJG.0b013e31815c3ab7","article-title":"Long-term relationship between intraocular pressure and visual field loss in primary open-angle glaucoma.","volume":"17","author":"Inatani","year":"2008","journal-title":"J. Glaucoma"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1002\/jnr.24899","article-title":"A multielectrode array-based hypoxia model for the analysis of electrical activity in murine retinae.","volume":"99","author":"Ingensiep","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1167\/iovs.05-0925","article-title":"Quantitative correlation of optic nerve pathology with ocular pressure and corneal thickness in the DBA\/2 mouse model of glaucoma.","volume":"47","author":"Inman","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6414","DOI":"10.1167\/iovs.09-5127","article-title":"Effects of acutely elevated hydrostatic pressure in a rat ex vivo retinal preparation.","volume":"51","author":"Ishikawa","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"33886","DOI":"10.1038\/srep33886","article-title":"24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure.","volume":"6","author":"Ishikawa","year":"2016","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s10633-006-9038-5","article-title":"Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human ERG.","volume":"114","author":"Janaky","year":"2007","journal-title":"Doc. Ophthalmol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1016\/j.visres.2008.04.016","article-title":"Activation of retinal ganglion cells in wild-type and rd1 mice through electrical stimulation of the retinal neural network.","volume":"48","author":"Jensen","year":"2008","journal-title":"Vision Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"8936","DOI":"10.1523\/JNEUROSCI.18-21-08936.1998","article-title":"The major cell populations of the mouse retina.","volume":"18","author":"Jeon","year":"1998","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.visres.2004.08.008","article-title":"Effects of elevated intraocular pressure on mouse retinal ganglion cells.","volume":"45","author":"Ji","year":"2005","journal-title":"Vision Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"5423","DOI":"10.1167\/iovs.06-0602","article-title":"RGC sensitivity to mild systemic hypoxia.","volume":"47","author":"Kergoat","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1038\/sj.eye.6702576","article-title":"Intraocular pressure measurement in mice: a comparison between Goldmann and rebound tonometry.","volume":"21","author":"Kim","year":"2007","journal-title":"Eye"},{"key":"B31","doi-asserted-by":"publisher","first-page":"828","DOI":"10.3109\/02713683.2010.494240","article-title":"Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL\/6 mouse eyes.","volume":"35","author":"Kipfer-Kauer","year":"2010","journal-title":"Curr. Eye Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1167\/iovs.10-6019\/-\/DCSupplemental","article-title":"Outflow physiology of the mouse eye: pressure dependence and washout.","volume":"52","author":"Lei","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1001\/archopht.1997.01100160221012","article-title":"Distribution of intraocular pressure. The Barbados Eye Study.","volume":"115","author":"Leske","year":"1997","journal-title":"Arch. Ophthalmol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1001\/archopht.121.1.48","article-title":"Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial.","volume":"121","author":"Leske","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"B35","first-page":"4169","article-title":"RGC death in mice after optic nerve crush injury: oxidative stress and neuroprotection.","volume":"41","author":"Levkovitch-Verbin","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1096\/fj.03-0739com","article-title":"Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer\u2019s disease and other neurological disorders.","volume":"18","author":"Louzada","year":"2004","journal-title":"FASEB J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1111\/j.1471-4159.1974.tb04313.x","article-title":"Free amino acids in developing rat retina.","volume":"22","author":"Macaione","year":"1974","journal-title":"J. Neurochem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.neuron.2011.06.025","article-title":"Rapid plasticity of visual responses in the adult lateral geniculate nucleus.","volume":"71","author":"Moore","year":"2011","journal-title":"Neuron"},{"key":"B39","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.exer.2005.01.008","article-title":"A new experimental model of glaucoma in rats through intracameral injections of hyaluronic acid.","volume":"81","author":"Moreno","year":"2005","journal-title":"Exp. Eye Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0115591","DOI":"10.1371\/journal.pone.0115591","article-title":"Hydrostatic pressure does not cause detectable changes in survival of human retinal ganglion cells.","volume":"10","author":"Osborne","year":"2015","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.preteyeres.2003.12.001","article-title":"Retinal ischemia: mechanisms of damage and potential therapeutic strategies.","volume":"23","author":"Osborne","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"9240","DOI":"10.1523\/JNEUROSCI.0940-16.2016","article-title":"Selective vulnerability of specific retinal ganglion cell types and synapses after transient ocular hypertension.","volume":"36","author":"Ou","year":"2016","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1073\/pnas.1419921112","article-title":"Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice.","volume":"112","author":"Pang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1109\/EMBC.2015.7319110","article-title":"Degeneration stage-specific response pattern of retinal ganglion cell spikes in rd10 mouse retina.","volume":"2015","author":"Park","year":"2015","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1038\/s41598-019-39141-1","article-title":"Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice.","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/BF00965643","article-title":"Taurine activation of a bicarbonate-dependent, ATP-supported calcium uptake in frog rod outer segments.","volume":"7","author":"Pasantes-Morales","year":"1982","journal-title":"Neurochem. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1136\/bjo.80.5.389","article-title":"Number of people with glaucoma worldwide.","volume":"80","author":"Quigley","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"B48","doi-asserted-by":"publisher","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":"B49","doi-asserted-by":"publisher","first-page":"8859","DOI":"10.1073\/pnas.1706994114","article-title":"Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse.","volume":"114","author":"Sabharwal","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B50","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1146\/annurev-neuro-071714-034120","article-title":"The types of retinal ganglion cells: current status and implications for neuronal classification.","volume":"38","author":"Sanes","year":"2015","journal-title":"Annu. Rev. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1167\/iovs.09-3947","article-title":"The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice.","volume":"51","author":"Sappington","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1167\/iovs.08-2321","article-title":"TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure.","volume":"50","author":"Sappington","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B53","first-page":"3300","article-title":"Acid-sensing ion channel 1a is involved in retinal ganglion cell death induced by hypoxia.","volume":"17","author":"Tan","year":"2011","journal-title":"Mol. Vis."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1523\/JNEUROSCI.2085-18.2019","article-title":"Mild Intraocular pressure elevation in mice reveals distinct retinal ganglion cell functional thresholds and pressure-dependent properties.","volume":"39","author":"Tao","year":"2019","journal-title":"J. Neurosci."},{"key":"B55","doi-asserted-by":"publisher","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":"B56","doi-asserted-by":"publisher","first-page":"4184","DOI":"10.1038\/s41598-021-83669-0","article-title":"Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout.","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"B57","doi-asserted-by":"publisher","first-page":"642176","DOI":"10.3389\/fnins.2021.642176","article-title":"Knock-Out of Tenascin-C ameliorates ischemia-induced rod-photoreceptor degeneration and retinal dysfunction.","volume":"15","author":"Wiemann","year":"2021","journal-title":"Front. Neurosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e72282","DOI":"10.1371\/journal.pone.0072282","article-title":"Retinal ganglion cell dendritic atrophy in DBA\/2J glaucoma.","volume":"8","author":"Williams","year":"2013","journal-title":"PLoS One"},{"key":"B59","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1085\/jgp.77.6.667","article-title":"Glycolytic and oxidative metabolism in relation to retinal function.","volume":"77","author":"Winkler","year":"1981","journal-title":"J. Gen. Physiol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.831392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T14:16:19Z","timestamp":1643724979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.831392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":59,"alternative-id":["10.3389\/fnins.2022.831392"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.831392","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]},"article-number":"831392"}}