{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:23:29Z","timestamp":1760149409582,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["9122-00104","NNF20OC0066152","R345-2020-1977"],"award-info":[{"award-number":["9122-00104","NNF20OC0066152","R345-2020-1977"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["9122-00104","NNF20OC0066152","R345-2020-1977"],"award-info":[{"award-number":["9122-00104","NNF20OC0066152","R345-2020-1977"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["9122-00104","NNF20OC0066152","R345-2020-1977"],"award-info":[{"award-number":["9122-00104","NNF20OC0066152","R345-2020-1977"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 \u00b5M or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV\u2013ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells12151987","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:57:33Z","timestamp":1690973853000},"page":"1987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intraocular Adeno-Associated Virus-Mediated Transgene Endothelin-1 Delivery to the Rat Eye Induces Functional Changes Indicative of Retinal Ischemia\u2014A Potential Chronic Glaucoma Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Karin M. L.","family":"Nordahl","sequence":"first","affiliation":[{"name":"Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadim","family":"Fedulov","sequence":"additional","affiliation":[{"name":"Clinical and Medical Affairs, Radiometer, 2700 Br\u00f8nsh\u00f8j, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Holm","sequence":"additional","affiliation":[{"name":"Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, 2600 Glostrup, Denmark"},{"name":"Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, 2450 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-8957","authenticated-orcid":false,"given":"Kristian A.","family":"Haanes","sequence":"additional","affiliation":[{"name":"Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/S0140-6736(17)31469-1","article-title":"Glaucoma","volume":"390","author":"Jonas","year":"2017","journal-title":"Lancet"},{"key":"ref_2","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."},{"doi-asserted-by":"crossref","unstructured":"Collaborative Normal-Tension Glaucoma Study Group (1998). Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am. J. Ophthalmol., 126, 487\u2013497.","key":"ref_3","DOI":"10.1016\/S0002-9394(98)00223-2"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/s41433-018-0042-2","article-title":"Normal tension glaucoma: Review of current understanding and mechanisms of the pathogenesis","volume":"32","author":"Killer","year":"2018","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/j.survophthal.2007.08.012","article-title":"What is the present pathogenetic concept of glaucomatous optic neuropathy?","volume":"52","author":"Flammer","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6652","DOI":"10.1167\/iovs.10-5490","article-title":"Retrobulbar blood flow velocities in open angle glaucoma and their association with mean arterial blood pressure","volume":"51","author":"Vass","year":"2010","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ajo.2008.04.034","article-title":"Retinal blood flow and nerve fiber layer measurements in early-stage open-angle glaucoma","volume":"146","author":"Berisha","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.1167\/iovs.10-6710","article-title":"Systemic vascular dysregulation and retrobulbar hemodynamics in normal-tension glaucoma","volume":"52","author":"Galassi","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.ophtha.2007.10.026","article-title":"Glaucoma is associated with peripheral vascular endothelial dysfunction","volume":"115","author":"Su","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1111\/aos.12298","article-title":"Ocular perfusion pressure in glaucoma","volume":"92","author":"Costa","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1167\/iovs.09-4867","article-title":"Distribution of ocular perfusion pressure and its relationship with open-angle glaucoma: The singapore malay eye study","volume":"51","author":"Zheng","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2019.04.001","article-title":"Retinal oximetry: Metabolic imaging for diseases of the retina and brain","volume":"70","author":"Olafsdottir","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","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":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00061198-200206000-00016","article-title":"Endothelin: Is it a contributor to glaucoma pathophysiology?","volume":"11","author":"Yorio","year":"2002","journal-title":"J. Glaucoma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00947082","article-title":"Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract","volume":"235","author":"Noske","year":"1997","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","first-page":"782","article-title":"Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma","volume":"31","author":"Mihaylova","year":"2017","journal-title":"Biotechnol. Biotechnol. Equip."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1167\/iovs.05-0240","article-title":"Altered endothelin-1 vasoreactivity in patients with untreated normal-pressure glaucoma","volume":"47","author":"Henry","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1136\/bjo.86.2.227","article-title":"Systemic vascular endothelial cell dysfunction in normal pressure glaucoma","volume":"86","author":"Buckley","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.exer.2006.03.007","article-title":"Intravitreal injection of endothelin-1 caused optic nerve damage following to ocular hypoperfusion in rabbits","volume":"83","author":"Sasaoka","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1016\/S0039-6257(99)00068-5","article-title":"Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia","volume":"44","author":"Oku","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C1495","DOI":"10.1152\/ajpcell.2001.281.5.C1495","article-title":"Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes","volume":"281","author":"Leonova","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1167\/iovs.05-0785","article-title":"Endothelin-1 enhances glutamate-induced retinal cell death, possibly through ETA receptors","volume":"46","author":"Kobayashi","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"doi-asserted-by":"crossref","unstructured":"Cheung, S.S.F., Leung, J.W.C., Lam, A.K.M., Lam, K.S.L., Chung, S.S.M., Lo, A.C.Y., and Chung, S.K. (2011). Selective over-expression of endothelin-1 in endothelial cells exacerbates inner retinal edema and neuronal death in ischemic retina. PLoS ONE, 6.","key":"ref_23","DOI":"10.1371\/journal.pone.0026184"},{"doi-asserted-by":"crossref","unstructured":"McGrady, N.R., Minton, A.Z., Stankowska, D.L., He, S., Jefferies, H.B., and Krishnamoorthy, R.R. (2017). Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma. BMC Neurosci., 18.","key":"ref_24","DOI":"10.1186\/s12868-017-0346-3"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.exer.2008.09.009","article-title":"Increase in endothelin B receptor expression in optic nerve astrocytes in endothelin-1 induced chronic experimental optic neuropathy","volume":"88","author":"Wang","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1167\/iovs.07-1243","article-title":"Acute endothelin-1 application induces reversible fast axonal transport blockade in adult rat optic nerve","volume":"49","author":"Wang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","first-page":"2704","article-title":"Human optic nerve head astrocytes as a target for endothelin-1","volume":"43","author":"Prasanna","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R1288","DOI":"10.1152\/ajpregu.00397.2010","article-title":"The interaction between endothelin-1 and nitric oxide in the vasculature: New perspectives","volume":"300","author":"Bourque","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_29","first-page":"568","article-title":"Vascular reactivity of optic nerve head and retinal blood vessels in glaucoma\u2014A review","volume":"17","author":"Venkataraman","year":"2010","journal-title":"Microcirculation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.3109\/02713689508995821","article-title":"An in vivo model of chronic optic nerve ischemia: The dose-dependent effects of endothelin-1 on the optic nerve microvasculature","volume":"14","author":"Cioffi","year":"1995","journal-title":"Curr. Eye Res."},{"key":"ref_31","first-page":"1860","article-title":"An endothelin-1 induced model of optic nerve ischemia in the rabbit","volume":"37","author":"Cioffi","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","first-page":"1085","article-title":"A model of retinal ischemia-reperfusion injury in rats by subconjunctival injection of endothelin-1","volume":"231","author":"Masuzawa","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1167\/iovs.03-0687","article-title":"Model of endothelin-1-induced chronic optic neuropathy in rat","volume":"45","author":"Chauhan","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","first-page":"596","article-title":"The in vivo effect of endothelins on retinal circulation in nondiabetic and diabetic rats","volume":"36","author":"Bursell","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1167\/iovs.13-13056","article-title":"OCT evaluation of neuroprotective effects of tafluprost on retinal injury after intravitreal injection of endothelin-1 in the rat eye","volume":"55","author":"Nagata","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.exer.2005.06.002","article-title":"Effects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat","volume":"82","author":"Lau","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1134\/S1819712419010045","article-title":"Dose-Dependent Effects of Endothelin-1 on Retinal and Optic Nerve Morphology in Sprague Dawley Rats","volume":"13","author":"Arfuzir","year":"2019","journal-title":"Neurochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1167\/iovs.12-9999","article-title":"Progressive retinal degeneration in transgenic mice with overexpression of endothelin-1 in vascular endothelial cells","volume":"53","author":"Mi","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s10633-011-9269-y","article-title":"Post-receptoral contributions to the rat scotopic electroretinogram a-wave","volume":"122","author":"Dang","year":"2011","journal-title":"Doc. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1113\/jphysiol.2002.030304","article-title":"Rod and cone contributions to the a-wave of the electroretinogram of the macaque","volume":"547","author":"Robson","year":"2003","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1023\/A:1001891904176","article-title":"Dissecting the dark-adapted electroretinogram","volume":"95","author":"Robson","year":"1998","journal-title":"Doc. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1017\/S0952523803205071","article-title":"Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors","volume":"20","author":"Eysteinsson","year":"2003","journal-title":"Vis. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1017\/S0952523804214043","article-title":"Origins of the electroretinogram oscillatory potentials in the rabbit retina","volume":"21","author":"Dong","year":"2004","journal-title":"Vis. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0024-3205(69)90283-5","article-title":"Synthetic interstial fluid for isolated mammalian tissue","volume":"8","author":"Bretag","year":"1969","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/s41598-018-19969-9","article-title":"In vivo imaging of adeno-associated viral vector labelled retinal ganglion cells","volume":"8","author":"Smith","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e6317","DOI":"10.7717\/peerj.6317","article-title":"Evaluation of AAV-DJ vector for retinal gene therapy","volume":"7","author":"Katada","year":"2019","journal-title":"PeerJ"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1046\/j.1442-9071.2003.00693.x","article-title":"Quantitative model demonstrating that recombinant adeno-associated virus and green fluorescent protein are non-toxic to the rat retina","volume":"31","author":"Daniels","year":"2003","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1089\/jop.2000.16.393","article-title":"Endothelin-1-mediated retinal artery vasospasm and the rabbit electroretinogram","volume":"16","author":"Ciulla","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/BF02044235","article-title":"A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits","volume":"231","author":"Takei","year":"1993","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0034-5288(18)31228-1","article-title":"Retinal vascular patterns in domestic animals","volume":"47","author":"Simoens","year":"1989","journal-title":"Res. Vet. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e11665","DOI":"10.7717\/peerj.11665","article-title":"Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion","volume":"9","author":"Lee","year":"2021","journal-title":"PeerJ"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1167\/iovs.11-8160","article-title":"Ligation of the pterygopalatine and external carotid arteries induces ischemic damage in the murine retina","volume":"52","author":"Ogishima","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"unstructured":"Zhong, L. (2021, January 1\u20137). Electroretinography (ERG) amplitude changes in a rat retinal ischemia model. Proceedings of the 2021 ARVO Annual Meeting, Online.","key":"ref_53"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/00041327-200103000-00015","article-title":"Functional and morphologic comparison of two methods to produce transient retinal ischemia in the rat","volume":"21","author":"Rosenbaum","year":"2001","journal-title":"J. Neuroophthalmol."},{"key":"ref_55","first-page":"33","article-title":"Electroretinographic findings in patients with central retinal vein occlusion","volume":"15","author":"Chenda","year":"2009","journal-title":"J. Soonchunhyang Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12146","DOI":"10.1038\/s41598-020-68957-5","article-title":"Correlation of electroretinography components with visual function and prognosis of central retinal artery occlusion","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1167\/iovs.02-0600","article-title":"Functional characterization of retina and optic nerve after acute ocular ischemia in rats","volume":"44","author":"Grozdanic","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1006\/exer.2001.1004","article-title":"Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure","volume":"72","author":"Bayer","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3109\/02713688709025202","article-title":"Changes in the oscillatory potentials of the electroretinogram in glaucoma","volume":"6","author":"Gur","year":"1987","journal-title":"Curr. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF00161371","article-title":"Selective reduction of oscillatory potentials and pattern electroretinograms after retinal ganglion cell damage by disease in humans or by kainic acid toxicity in cats","volume":"77","author":"Vaegan","year":"1991","journal-title":"Doc. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/ICU.0000000000000241","article-title":"Electroretinography in glaucoma diagnosis","volume":"27","author":"Wilsey","year":"2016","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1136\/bjo.34.9.550","article-title":"The electroretinogram in glaucomatous eyes","volume":"34","author":"Leydhecker","year":"1950","journal-title":"Br. J. Ophthalmol."},{"key":"ref_63","first-page":"200","article-title":"Primary open-angle glaucoma is not associated with photoreceptor loss","volume":"36","author":"Kendell","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1136\/bjo.85.4.397","article-title":"The a-wave of the dark adapted electroretinogram in glaucomas: Are photoreceptors affected?","volume":"85","author":"Velten","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1136\/bjo.2010.183756","article-title":"Evidence of outer retinal changes in glaucoma patients as revealed by ultrahigh-resolution in vivo retinal imaging","volume":"95","author":"Choi","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.exer.2015.01.006","article-title":"Laser-induced ocular hypertension in adult rats does not affect non-RGC neurons in the ganglion cell layer but results in protracted severe loss of cone-photoreceptors","volume":"132","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0014-4835(05)80011-9","article-title":"Flash and pattern electroretinogram changes with optic atrophy and glaucoma","volume":"60","author":"Vaegan","year":"1995","journal-title":"Exp. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00061198-199702000-00006","article-title":"Widespread choroidal insufficiency in primary open-angle glaucoma","volume":"6","author":"Yin","year":"1997","journal-title":"J. Glaucoma"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1471-4159.1992.tb08912.x","article-title":"Glutamate release in experimental ischaemia of the retina: An approach using microdialysis","volume":"59","author":"Dias","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0014-2999(98)00317-3","article-title":"Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina","volume":"350","author":"Adachi","year":"1998","journal-title":"Eur. J. Pharmacol."},{"doi-asserted-by":"crossref","unstructured":"Russo, R., Cavaliere, F., Varano, G.P., Milanese, M., Adornetto, A., Nucci, C., Bonanno, G., Morrone, L.A., Corasaniti, M.T., and Bagetta, G. (2013). Impairment of neuronal glutamate uptake and modulation of the glutamate transporter GLT-1 induced by retinal ischemia. PLoS ONE, 8.","key":"ref_71","DOI":"10.1371\/journal.pone.0069250"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1017\/S0952523803202017","article-title":"Involvement of glutamate in ischemic neurodegeneration in isolated retina","volume":"20","author":"Izumi","year":"2003","journal-title":"Vis. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jpain.2009.01.265","article-title":"Early and late contributions of glutamate and CGRP to mechanical sensitization by endothelin-1","volume":"10","author":"Khodorova","year":"2009","journal-title":"J. Pain"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1046\/j.1471-4159.1997.68052194.x","article-title":"Endothelin evokes efflux of glutamate in cultures of rat astrocytes","volume":"68","author":"Sasaki","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/glia.10020","article-title":"Endothelin downregulates the glutamate transporter GLAST in cAMP-differentiated astrocytes in vitro","volume":"37","author":"Matsuura","year":"2002","journal-title":"Glia"},{"unstructured":"Kolb, H., Fernandez, E., and Nelson, R. (2005). Webvision: The Organization of the Retina and Visual System, University of Utah Health Sciences Center.","key":"ref_76"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1167\/iovs.03-0009","article-title":"Regional variations in local contributions to the primate photopic flash ERG: Revealed using the slow-sequence mfERG","volume":"44","author":"Rangaswamy","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1073\/pnas.95.8.4663","article-title":"Functions of the two glutamate transporters GLAST and GLT-1 in the retina","volume":"95","author":"Harada","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1136\/bjo.64.11.818","article-title":"Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia","volume":"64","author":"Hayreh","year":"1980","journal-title":"Br. J. Ophthalmol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0006-8993(95)00193-T","article-title":"Redistribution of GABA immunoreactivity following central retinal artery occlusion","volume":"677","author":"Barnett","year":"1995","journal-title":"Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/bjo.2007.133223","article-title":"Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model","volume":"92","author":"Holcombe","year":"2008","journal-title":"Br. J. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"PL111","DOI":"10.1016\/0024-3205(93)90707-A","article-title":"Analysis of vasocontractile responses to endothelin-1 in rabbit retinal vessels using an ETA receptor antagonist and an ETB receptor agonist","volume":"53","author":"Takei","year":"1993","journal-title":"Life Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1167\/iovs.08-3129","article-title":"Functional and molecular characterization of the endothelin system in retinal arterioles","volume":"50","author":"Hein","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/01.HYP.36.6.1002","article-title":"Heterozygous knock-Out of ETB receptors induces BQ-123-sensitive hypertension in the mouse","volume":"36","author":"Berthiaume","year":"2000","journal-title":"Hypertension"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/01.CIR.97.8.752","article-title":"Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade","volume":"97","author":"Verhaar","year":"1998","journal-title":"Circulation"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/glia.1036","article-title":"Role of the astrocytic ETB receptor in the regulation of extracellular endothelin-1 during hypoxia","volume":"34","author":"Hasselblatt","year":"2001","journal-title":"Glia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1006\/bbrc.1994.1395","article-title":"Clearance of circulating endothelin-1 by ETB receptors in rats","volume":"199","author":"Fukuroda","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1006\/exnr.1997.6468","article-title":"Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans","volume":"145","author":"Rogers","year":"1997","journal-title":"Exp. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/(SICI)1098-1136(199905)26:3<268::AID-GLIA8>3.0.CO;2-G","article-title":"BQ788, an endothelin ETB receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain","volume":"26","author":"Koyama","year":"1999","journal-title":"Glia"},{"doi-asserted-by":"crossref","unstructured":"Minton, A.Z., Phatak, N.R., Stankowska, D.L., He, S., Ma, H.-Y., Mueller, B.H., Jiang, M., Luedtke, R., Yang, S., and Brownlee, C. (2012). Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. PLoS ONE, 7.","key":"ref_90","DOI":"10.1371\/journal.pone.0043199"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1001\/archopht.1994.01090210119024","article-title":"Endothelin receptor-binding subtypes in the human retina and choroid","volume":"112","author":"MacCumber","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","article-title":"CGRP as the target of new migraine therapies\u2014Successful translation from bench to clinic","volume":"14","author":"Edvinsson","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_93","first-page":"S102","article-title":"CGRP: A novel neuropeptide from the calcitonin gene is the most potent vasodilator known","volume":"4","author":"Tippins","year":"1986","journal-title":"J. Hypertens. Suppl."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1124\/jpet.109.155143","article-title":"Calcitonin gene-related peptide selectively relaxes contractile responses to endothelin-1 in rat mesenteric resistance arteries","volume":"331","author":"Meens","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"doi-asserted-by":"crossref","unstructured":"Meens, M.J.P.M.T., Compeer, M.G., Hackeng, T.M., van Zandvoort, M.A., Janssen, B.J.A., and De Mey, J.G.R. (2010). Stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by CGRP and dissociation of ET-1\/ETA-receptor complexes. PLoS ONE, 5.","key":"ref_95","DOI":"10.1371\/journal.pone.0010917"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"H1868","DOI":"10.1152\/ajpheart.00241.2004","article-title":"Prevention of endothelin-1-induced increases in blood pressure: Role of endogenous CGRP","volume":"287","author":"Wang","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neulet.2011.06.049","article-title":"Endogenous CGRP protects retinal cells against stress induced apoptosis in rats","volume":"501","author":"Yang","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/NEN.0b013e31819ac71b","article-title":"Locally synthesized calcitonin gene-related Peptide has a critical role in peripheral nerve regeneration","volume":"68","author":"Toth","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.exer.2017.06.002","article-title":"Distribution of CGRP and its receptor components CLR and RAMP1 in the rat retina","volume":"161","author":"Blixt","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.expneurol.2011.12.027","article-title":"High pressure-induced retinal ischaemia reperfusion causes upregulation of gap junction protein connexin43 prior to retinal ganglion cell loss","volume":"234","author":"Kerr","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1152\/jn.01137.2015","article-title":"Retinal cross talk in the mammalian visual system","volume":"115","author":"Tang","year":"2016","journal-title":"J. Neurophysiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.exer.2015.03.015","article-title":"Retino-retinal projection in juvenile and young adult rats and mice","volume":"134","year":"2015","journal-title":"Exp. Eye Res."},{"doi-asserted-by":"crossref","unstructured":"Lucas-Ruiz, F., Galindo-Romero, C., Rodr\u00edguez-Ram\u00edrez, K.T., Vidal-Sanz, M., and Agudo-Barriuso, M. (2019). Neuronal Death in the Contralateral Un-Injured Retina after Unilateral Axotomy: Role of Microglial Cells. Int. J. Mol. Sci., 20.","key":"ref_103","DOI":"10.3390\/ijms20225733"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1475-1313.1994.tb00132.x","article-title":"Unilateral ocular vascular stress in man and retinal responsivity in the contralateral eye","volume":"14","author":"Kergoat","year":"1994","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12974-017-0982-7","article-title":"Microglial dynamics after axotomy-induced retinal ganglion cell death","volume":"14","year":"2017","journal-title":"J. Neuroinflamm."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/15\/1987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:24:25Z","timestamp":1760127865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/15\/1987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":105,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cells12151987"],"URL":"https:\/\/doi.org\/10.3390\/cells12151987","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}