{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:25Z","timestamp":1791267145254,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T00:00:00Z","timestamp":1598659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center, Poland","award":["PRELUDIUM no 2016\/23\/N\/NZ7\/ 02555"],"award-info":[{"award-number":["PRELUDIUM no 2016\/23\/N\/NZ7\/ 02555"]}]},{"name":"Statutory Funds Nencki Institute, Poland","award":["400.1"],"award-info":[{"award-number":["400.1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury (ONI) or laser-induced ocular hypertension (OHT). In models of glaucoma, BDNF therapy can delay or halt RGCs loss, but this protection is time-limited. The decreased efficacy of BDNF supplementation has been in part attributed to BDNF TrkB receptor downregulation. However, whether BDNF overexpression causes TrkB downregulation, impairing long-term BDNF signaling in the retina, has not been conclusively proven. After ONI or OHT, when increased retinal BDNF was detected, a concomitant increase, no change or a decrease in TrkB was reported. We examined quantitatively the retinal concentrations of the TrkB protein in relation to BDNF, in a course of adeno-associated viral vector gene therapy (AAV2-BDNF), using a microbead trabecular occlusion model of glaucoma. We show that unilateral glaucoma, with intraocular pressure ( IOP) increased for five weeks, leads to a bilateral decrease of BDNF in the retina at six weeks, accompanied by up to four-fold TrkB upregulation, while a moderate BDNF overexpression in a glaucomatous eye triggers changes that restore normal TrkB concentrations, driving signaling towards long-term RGCs neuroprotection. We conclude that for glaucoma therapy, the careful selection of the appropriate BDNF concentration is the main factor securing the long-term responsiveness of RGCs and the maintenance of normal TrkB levels.<\/jats:p>","DOI":"10.3390\/ijms21176262","type":"journal-article","created":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T06:06:22Z","timestamp":1598767582000},"page":"6262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma"],"prefix":"10.3390","volume":"21","author":[{"given":"Anna","family":"W\u00f3jcik-Gryciuk","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"},{"name":"Mediq Clinic, 05-120 Legionowo, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Gajewska-Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Group of Restorative Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4425-8009","authenticated-orcid":false,"given":"Katarzyna","family":"Kordecka","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7210-6950","authenticated-orcid":false,"given":"Pawe\u0142 M.","family":"Boguszewski","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioletta","family":"Waleszczyk","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2605-0124","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Skup","sequence":"additional","affiliation":[{"name":"Group of Restorative Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0306-3623(97)00361-3","article-title":"Immunohistochemical distribution of neurotrophins and their receptors in the rat retina and the effects of ischemia and reperfusion","volume":"30","author":"Vecino","year":"1998","journal-title":"Gen. 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