{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:25:00Z","timestamp":1790270700524,"version":"4.1.0"},"reference-count":89,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u20102019\u201012369119"],"award-info":[{"award-number":["RF\u20102019\u201012369119"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008245","name":"Center for Neuroscience Research","doi-asserted-by":"publisher","award":["FOE D.M 571\/2022"],"award-info":[{"award-number":["FOE D.M 571\/2022"]}],"id":[{"id":"10.13039\/100008245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Retinal ganglion cells (RGCs) are the output stage of retinal information processing, via their axons forming the optic nerve (ON). ON damage leads to axonal degeneration and death of RGCs, and results in vision impairment. Nerve growth factor (NGF) signalling is crucial for RGC operations and visual functions. Here, we investigate a new neuroprotective mechanism of a novel therapeutic candidate, a p75\u2010less, TrkA\u2010biased NGF agonist (hNGFp) in rat RGC degeneration, in comparison with wild type human NGF (hNGFwt).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Both neonate and adult rats, whether subjected or not to ON lesion, were treated with intravitreal injections or eye drops containing either hNGFp or hNGFwt. Different doses of the drugs were administered at days 1, 4 or 7 after injury for a maximum of 10\u00a0days, when immunofluorescence, electrophysiology, cellular morphology, cytokine array and behaviour studies were carried out. Pharmacokinetic evaluation was performed on rabbits treated with hNGFp ocular drops.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>hNGFp exerted a potent RGC neuroprotection by acting on microglia cells, and outperformed hNGFwt in rescuing RGC degeneration and reducing inflammatory molecules. Delayed use of hNGFp after ON lesion resulted in better outcomes compared with treatment with hNGFwt. Moreover, hNGFp\u2010based ocular drops were less algogenic than hNGFwt. Pharmacokinetic measurements revealed that biologically relevant quantities of hNGFp were found in the rabbit retina.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data point to microglia as a new cell target through which NGF\u2010induced TrkA signalling exerts neuroprotection of the RGC, emphasizing hNGFp as a powerful treatment to tackle retinal degeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17316","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T06:28:59Z","timestamp":1725949739000},"page":"4890-4919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A p75 neurotrophin receptor\u2010sparing nerve growth factor protects retinal ganglion cells from neurodegeneration by targeting microglia"],"prefix":"10.1111","volume":"181","author":[{"given":"Laura","family":"Latini","sequence":"first","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Souza Monteiro","family":"De Araujo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology and Oncology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Canovai","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Buccarello","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Logu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology and Oncology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Novelli","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience  Italian National Research Council\u2013CNR Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Vlasiuk","sequence":"additional","affiliation":[{"name":"Faculty of Biosciences Collaboration for Joint PhD Degree Between EMBL and Heidelberg University  Heidelberg Germany"},{"name":"Epigenetics and Neurobiology Unit, EMBL Rome European Molecular Biology Laboratory  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Malerba","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Arisi","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Florio","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Asari","sequence":"additional","affiliation":[{"name":"Faculty of Biosciences Collaboration for Joint PhD Degree Between EMBL and Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Capsoni","sequence":"additional","affiliation":[{"name":"BIO@SNS Laboratory Scuola Normale Superiore  Pisa Italy"},{"name":"Section of Human Physiology, Department of Neuroscience and Rehabilitation University of Ferrara  Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Strettoi","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience  Italian National Research Council\u2013CNR Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino","family":"Villetti","sequence":"additional","affiliation":[{"name":"Department of Research &amp; Development Chiesi Farmaceutici  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Pietro","family":"Imbimbo","sequence":"additional","affiliation":[{"name":"Department of Research &amp; Development Chiesi Farmaceutici  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5181-4456","authenticated-orcid":false,"given":"Massimo","family":"Dal Monte","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-8395","authenticated-orcid":false,"given":"Romina","family":"Nassini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology and Oncology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Geppetti","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology and Oncology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2620-8371","authenticated-orcid":false,"given":"Silvia","family":"Marinelli","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"European Brain Research Institute\u2010Fondazione Rita Levi\u2010Montalcini  Rome Italy"},{"name":"BIO@SNS Laboratory Scuola Normale Superiore  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.17.2215"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.147801"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08446-0"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01437-w"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04496.x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200010)32:1<91::AID-GLIA90>3.0.CO;2-X"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2018.02.022"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510645103"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12461"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.773347"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017321"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww271"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(91)90097-V"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-22-09687.1999"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1078"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3RI0615-239R"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.4415\/ANN_11_03_08"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101568"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.11.146"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","unstructured":"CZI Single\u2010Cell Biology Program.Abdulla S. Aevermann B. Assis P. Badajoz S. Bell S. M. Bezzi E. Cakir B. Chaffer J. Chambers S. &Cherry J. M.(2023).CZ CELL\u00d7GENE Discover: A single\u2010cell data platform for scalable exploration analysis and modeling of aggregated data.https:\/\/doi.org\/10.1101\/2023.10.30.563174.","DOI":"10.1101\/2023.10.30.563174"},{"issue":"4","key":"e_1_2_13_22_1","first-page":"386","article-title":"Evaluation of five agents\/methods for anesthesia of neonatal rats","volume":"47","author":"Danneman P. J.","year":"1997","journal-title":"Laboratory Animal Science"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(94)90189-9"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.12.019"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1102-1131"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh096"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000017069"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv366"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80432-8"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/383166a0"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-07-02318.1996"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.08.009"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2016.11.005"},{"key":"e_1_2_13_34_1","first-page":"225","article-title":"Multilayered retinal microglial response to optic nerve transection in rats","volume":"11","author":"Garcia\u2010Valenzuela E.","year":"2005","journal-title":"Molecular Vision"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60427-2"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000431128"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(02)00332-9"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2018.1515917"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002974"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00266"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1133"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00044"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202300446"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02343055"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906678106"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02332863"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.23.11249"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.12.005"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065057"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-05-02136.1993"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2023.2251389"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4340"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.09.003"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.7.2861"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1177\/24725552211000672"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136425"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.07.014"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1631"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15292"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90695-J"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112889"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112929"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.08.020"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90565-7"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2018.05.006"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4295"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23312"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2018-312470"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9658-2_2"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.026"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(95)00043-D"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20360"},{"key":"e_1_2_13_75_1","first-page":"3232","article-title":"Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia","volume":"34","author":"Siliprandi R.","year":"1993","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-vision-091517-034425"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/368246a0"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101760RR"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00455.1993"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad282"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.11.006"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112476"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480240103"},{"key":"e_1_2_13_84_1","first-page":"437","article-title":"Neurotrophins in the developing and regenerating visual system","volume":"13","author":"Bartheld C. S.","year":"1998","journal-title":"Histology and Histopathology"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2004.047910"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34518"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-09-03273.1998"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1224"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505298"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6182-11.2012"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.17316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T06:25:03Z","timestamp":1730701503000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.17316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,9]]},"references-count":89,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/bph.17316"],"URL":"https:\/\/doi.org\/10.1111\/bph.17316","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,9]]},"assertion":[{"value":"2024-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}