{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:48:17Z","timestamp":1782978497729,"version":"3.54.5"},"reference-count":55,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2019,7]]},"DOI":"10.1016\/j.neuroscience.2019.05.021","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T08:39:27Z","timestamp":1558600767000},"page":"119-129","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Eye Drop Instillation of the Rac1 Modulator CNF1 Attenuates Retinal Gliosis and Ameliorates Visual Performance in a Rat Model of Hypertensive Retinopathy"],"prefix":"10.1016","volume":"411","author":[{"given":"Andrea","family":"Matteucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ricceri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Fabbri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fortuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Travaglione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Guidotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Villa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Pricci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaira","family":"Maroccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Campana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Malchiodi-Albedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Fiorentini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Loizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2019.05.021_bb0005","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1124\/dmd.30.4.421","article-title":"Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes","volume":"30","author":"Acheampong","year":"2002","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0010","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/AJP.0b013e31827a72d2","article-title":"Botulinum toxin a in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial","volume":"29","author":"Apalla","year":"2013","journal-title":"Clin J Pain"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0015","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1167\/iovs.05-0446","article-title":"Light-induced photoreceptor degeneration in the mouse involves activation of the small GTPase Rac1","volume":"47","author":"Belmonte","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0020","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"M\u00fcller cells in the healthy and diseased retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0025","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/jhh.2015.112","article-title":"From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency.","volume":"30","author":"Cremer","year":"2016","journal-title":"J Hum Hypertens"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0030","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1167\/iovs.16-20072","article-title":"Topical delivery of anti-VEGF drugs to the ocular posterior segment using cell-penetrating peptides","volume":"58","author":"de Cogan","year":"2017","journal-title":"Investig Opthalmology Vis Sci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0035","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/npp.2011.301","article-title":"Modulation of RhoGTPases improves the behavioral phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome","volume":"37","author":"De Filippis","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0040","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.euroneuro.2015.03.012","article-title":"Modulation of rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome","volume":"25","author":"De Filippis","year":"2015","journal-title":"Eur Neuropsychopharmacol"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0045","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1471-4159.2010.07056.x","article-title":"Differential roles of ERK1\/2 and JNK in retinal development and degeneration","volume":"116","author":"Donovan","year":"2011","journal-title":"J Neurochem"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0050","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(02)01132-7","article-title":"CNF1 exploits the ubiquitin-proteasome machinery to restrict rho GTPase activation for bacterial host cell invasion","volume":"111","author":"Doye","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0055","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.3390\/toxins7114610","article-title":"Cell-to-cell propagation of the bacterial toxin CNF1 via extracellular vesicles: potential impact on the therapeutic use of the toxin","volume":"7","author":"Fabbri","year":"2015","journal-title":"Toxins (Basel)"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0060","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1111\/j.1365-2958.1993.tb01254.x","article-title":"Induction of phagocytic behaviour in human epithelial cells by Escherichia coli cytotoxic necrotizing factor type 1","volume":"9","author":"Falzano","year":"1993","journal-title":"Mol Microbiol"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0065","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1742-2094-9-92","article-title":"IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma","volume":"9","author":"Gallego","year":"2012","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0070","article-title":"The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa","volume":"6","author":"Guadagni","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0075","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1155\/NP.2004.241","article-title":"A chronic implant to record Electroretinogram, visual evoked potentials and oscillatory potentials in awake, freely moving rats for pharmacological studies","volume":"11","author":"Guarino","year":"2004","journal-title":"Neural Plast"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0080","doi-asserted-by":"crossref","first-page":"9397","DOI":"10.1073\/pnas.0808940106","article-title":"Depleting Rac1 in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function","volume":"106","author":"Haruta","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0085","first-page":"353","article-title":"Astrocytes in glaucomatous optic neuropathy","volume":"173","author":"Hernandez","year":"2008","journal-title":"In: Progress in brain research"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0090","first-page":"2934","article-title":"Retinal degeneration modulates intracellular localization of CDC42 in photoreceptors","volume":"17","author":"Heynen","year":"2011","journal-title":"Mol Vis"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0095","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/glia.20516","article-title":"Reactive nonproliferative gliosis predominates in a chronic mouse model of glaucoma","volume":"55","author":"Inman","year":"2007","journal-title":"Glia"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0100","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1074\/jbc.M116.748871","article-title":"A novel Rac1-GSPT1 signaling pathway controls Astrogliosis following central nervous system injury","volume":"292","author":"Ishii","year":"2017","journal-title":"J Biol Chem"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0105","first-page":"815","article-title":"Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy","volume":"47","author":"Lieth","year":"1998","journal-title":"Penn State Retina Research Group Diabetes"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0110","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.bbrc.2016.09.032","article-title":"RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis","volume":"479","author":"Liu","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0115","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/8da0f878-fcab-4f65-bad0-c5bdda8181ed","article-title":"CNF1 increases brain energy level, counteracts Neuroinflammatory markers and rescues cognitive deficits in a murine model of Alzheimer's disease","volume":"8","author":"Loizzo","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0120","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exer.2016.03.027","article-title":"Astrocyte structural reactivity and plasticity in models of retinal detachment","volume":"150","author":"Luna","year":"2016","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0125","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0034115","article-title":"CNF1 improves astrocytic ability to support neuronal growth and differentiation in vitro","volume":"7","author":"Malchiodi-Albedi","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0130","first-page":"175","article-title":"Histopathology of the human retina in retinitis pigmentosa","volume":"17","author":"Milam","year":"1998","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0135","doi-asserted-by":"crossref","unstructured":"Mizuno K, Ozawa K, Nishida S AK (1972) Hereditary retinal dystrophic rats in a strain of spontaneously hypertensive rat. In: Spontaneous Hypertension\u2014Its Pathogenesis and Complications (Okamoto K, ed), pp 23. Tokyo: Igaku Shoin Ltd.","DOI":"10.1007\/978-3-642-65441-1_5"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0140","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1053\/j.gastro.2011.04.057","article-title":"Single nucleotide polymorphisms that increase expression of the guanosine triphosphatase RAC1 are associated with ulcerative colitis","volume":"141","author":"Muise","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0145","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/SCS.0000000000002272","article-title":"Botulinum toxin a upregulates Rac1, Cdc42, and RhoA gene expression in a dose-dependent manner: In vivo and in vitro study","volume":"27","author":"Park","year":"2016","journal-title":"J Craniofac Surg"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0150","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.preteyeres.2008.05.001","article-title":"Vascular endothelial growth factor in eye disease","volume":"27","author":"Penn","year":"2008","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0155","doi-asserted-by":"crossref","first-page":"683","DOI":"10.3390\/toxins2040683","article-title":"Bacterial toxins and the nervous system: neurotoxins and multipotential toxins interacting with neuronal cells","volume":"2","author":"Popoff","year":"2010","journal-title":"Toxins (Basel)"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0160","series-title":"In: Photostasis and related phenomena","first-page":"93","article-title":"The origin of the major rod- and cone-driven components of the rodent Electroretinogram and the effect of age and light-rearing history on the magnitude of these components","author":"Pugh","year":"1998"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0165","first-page":"922","article-title":"The conflicting role of Rac1 in inflammation","volume":"2","author":"Qin","year":"2015","journal-title":"Inflamm Cell Signal"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0170","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.2174\/1570159X16666180412092859","article-title":"Nerve growth factor: early studies and recent clinical trials","volume":"16","author":"Rocco","year":"2018","journal-title":"Curr Neuropharmacol"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0175","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/0031-9384(93)90300-5","article-title":"Visual dysfunction in the spontaneously hypertensive rat","volume":"54","author":"Rogers","year":"1993","journal-title":"Physiol Behav"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0180","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1097\/00004872-200110000-00022","article-title":"Changes of retinal neurons and glial fibrillary acid protein immunoreactive astrocytes in spontaneously hypertensive rats","volume":"19","author":"Sabbatini","year":"2001","journal-title":"J Hypertens"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0185","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1081\/CEH-120015348","article-title":"Neuroprotective effect of treatment with calcium antagonists on hypertensive retina","volume":"24","author":"Sabbatini","year":"2002","journal-title":"Clin Exp Hypertens"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0190","doi-asserted-by":"crossref","first-page":"13669","DOI":"10.1074\/jbc.273.22.13669","article-title":"The rho-deamidating cytotoxic necrotizing factor 1 from Escherichia coli possesses transglutaminase activity. Cysteine 866 and histidine 881 are essential for enzyme activity","volume":"273","author":"Schmidt","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0195","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/02713680701435391","article-title":"Hypertension increases retinal inflammation in experimental diabetes: a possible mechanism for aggravation of diabetic retinopathy by hypertension","volume":"32","author":"Silva","year":"2007","journal-title":"Curr Eye Res"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0200","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0205","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0166348","article-title":"Retinal pre-conditioning by CD59a knockout protects against light-induced photoreceptor degeneration","volume":"11","author":"Song","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0210","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fncel.2014.00314","article-title":"Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration","volume":"8","author":"Stankiewicz","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0215","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/ejn.13965","article-title":"A journey into the retina: M\u00fcller glia commanding survival and death","volume":"47","author":"Subirada","year":"2018","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0220","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1167\/iovs.02-1136","article-title":"Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma","volume":"44","author":"Tezel","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0225","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0140495","article-title":"CNF1 enhances brain energy content and counteracts spontaneous epileptiform phenomena in aged DBA\/2J mice","volume":"10","author":"Travaglione","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0230","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1111\/febs.12874","article-title":"Enhancement of mitochondrial ATP production by the Escherichia coli cytotoxic necrotizing factor 1","volume":"281","author":"Travaglione","year":"2014","journal-title":"FEBS"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0235","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/sj.cdd.4401522","article-title":"Cytotoxic necrotizing factor 1 hinders skeletal muscle differentiation in vitro by perturbing the activation\/deactivation balance of rho GTPases","volume":"12","author":"Travaglione","year":"2005","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0240","unstructured":"Trivi\u00f1o, Ram\u00edrez, Salazar, Roja, de Hoz R (2005) Retinal changes in age-related macular degeneration. New York, NY, USA: Nova; 2005. pp. 1\u201337. In: Focus on Eye Research (Ioseliane OR, ed), pp 1\u201337. New York: Nova."},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0245","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1460-9568.2008.06322.x","article-title":"Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina","volume":"28","author":"VanGuilder","year":"2008","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0250","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.mcn.2015.08.001","article-title":"Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration","volume":"68","author":"Vigneswara","year":"2015","journal-title":"Mol Cell Neurosci"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0255","first-page":"1010","article-title":"Retinal degeneration in mature rats. Comparison of the disease in an Osborne-Mendel and a spontaneously hypertensive Wistar strain","volume":"13","author":"von Sallmann","year":"1974","journal-title":"Invest Ophthalmol"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0260","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0147733","article-title":"A comprehensive behavioral test battery to assess learning and memory in 129S6\/Tg2576 mice","volume":"11","author":"Wolf","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0265","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/bmb\/ldh050","article-title":"Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality","volume":"73-74","author":"Wong","year":"2005","journal-title":"Br Med Bull"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0270","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.brainresbull.2017.05.003","article-title":"Control of astrocyte morphology by rho GTPases","volume":"136","author":"Zeug","year":"2018","journal-title":"Brain Res Bull"},{"key":"10.1016\/j.neuroscience.2019.05.021_bb0275","first-page":"1732","article-title":"Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit","volume":"9","author":"Zhao","year":"2016","journal-title":"Int J Ophthalmol"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219303446?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219303446?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T04:02:39Z","timestamp":1562126559000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306452219303446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":55,"alternative-id":["S0306452219303446"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2019.05.021","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2019,7]]}}}