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In this study, we examined the effects of BNN27 on neural\/glial cell function, apoptosis, and inflammation in the experimental rat streptozotocin (STZ) model of diabetic retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate p75NTR expression was investigated. BNN27 (2,10, and 50 mg\/kg i.p. for 7 days) administration 4 weeks post\u2013STZ injection (paradigm A) reversed the diabetes-induced glial activation and loss of function of amacrine cells (brain nitric oxide synthetase\/tyrosine hydroxylase expression) and ganglion cell axons via a TrkA receptor (TrkAR)-dependent mechanism. BNN27 activated\/phosphorylated the TrkAY490 residue in the absence but not the presence of TrkAR inhibitor and abolished the diabetes-induced increase in p75NTR expression. However, it had no effect on retinal cell death (TUNEL+ cells). A similar result was observed when BNN27 (10 mg\/kg i.p.) was administered at the onset of diabetes, every other day for 4 weeks (paradigm B). However, BNN27 decreased the activation of caspase-3 in both paradigms. Finally, BNN27 reduced the proinflammatory (TNF\u03b1 and IL-1\u03b2) and increased the anti-inflammatory (IL-10 and IL-4) cytokine levels. These findings suggest that BNN27 has the pharmacological profile of a therapeutic for DR, since it targets both the neurodegenerative and inflammatory components of the disease.<\/jats:p>","DOI":"10.2337\/db17-0391","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T01:25:35Z","timestamp":1512523535000},"page":"321-333","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":38,"title":["The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With Streptozotocin-Induced Diabetes"],"prefix":"10.2337","volume":"67","author":[{"given":"Ruth","family":"Ib\u00e1n-Arias","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Lisa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niki","family":"Mastrodimou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Despina","family":"Kokona","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuil","family":"Koulakis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiota","family":"Iordanidou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonis","family":"Kouvarakis","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Chemical Processes, Department of Chemistry, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrto","family":"Fothiadaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Papadogkonaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aggeliki","family":"Sotiriou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haralambos E.","family":"Katerinopoulos","sequence":"additional","affiliation":[{"name":"Organic Chemistry, Department of Chemistry, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille","family":"Gravanis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"},{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research & Technology-Hellas, University of Crete, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Charalampopoulos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0187-9048","authenticated-orcid":false,"given":"Kyriaki","family":"Thermos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"2022031210273771700_B1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4103\/0301-4738.100542","article-title":"The worldwide epidemic of diabetic retinopathy","volume":"60","author":"Zheng","year":"2012","journal-title":"Indian J Ophthalmol"},{"key":"2022031210273771700_B2","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMra1005073","article-title":"Diabetic retinopathy","volume":"366","author":"Antonetti","year":"2012","journal-title":"N Engl J Med"},{"key":"2022031210273771700_B3","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1172\/JCI2425","article-title":"Neural apoptosis in the retina during experimental and human diabetes. 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