Melatonin prevents blood-retinal barrier breakdown and mitochondrial dysfunction in high glucose and hypoxia-induced in vitro diabetic macular edema model

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridKurtdere, Kardelen/0000-0002-4611-3436
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.authorwosidKurtdere, Kardelen/KEE-9234-2024
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorKurtdere, Kardelen
dc.contributor.authorGuclu, Hande
dc.contributor.authorChasan, Tourkian
dc.contributor.authorTurgut, Esra
dc.date.accessioned2024-06-12T10:59:27Z
dc.date.available2024-06-12T10:59:27Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractDiabetic macular edema (DME) is a leading cause of blindness in diabetic retinopathy. Prolonged hyperglycemia plus hypoxia contributes to DME pathogenesis. Retinal pigmented epithelial cells comprise the outer bloodretinal barrier and are essential for maintaining physiological functioning of the retina. Melatonin acts as an antioxidant and regulator of mitochondrial bioenergetics and has a protective effect against ocular diseases. However, the role of mitochondrial dysfunction and the therapeutic potential of melatonin in DME remain largely unexplored. Here, we used an in vitro model of DME to investigate blood-retinal barrier integrity and permeability, angiogenesis, mitochondrial dynamics, and apoptosis signaling to evaluate the potential protective efficacy of melatonin in DME. We found that melatonin prevents cell hyper-permeability and outer barrier breakdown by reducing HIF-1 alpha, HIF-1 beta and VEGF and VEGF receptor gene expression. In addition, melatonin reduced the expression of genes involved in mitochondrial fission (DRP1, hFis1, MIEF2, MFF), mitophagy (PINK, BNip3, NIX), and increased the expression of genes involved in mitochondrial biogenesis (PGC-1 alpha, NRF2, PPAR gamma) to maintain mitochondrial homeostasis. Moreover, melatonin prevented apoptosis of retinal pigmented epithelial cells. Our results suggest that mitochondrial dysfunction may be involved in DME pathology, and melatonin may have therapeutic value in DME, by targeting signaling in mitochondria.en_US
dc.description.sponsorshipTrakya University Scientific Research Fund [TUBAP 2018/197]en_US
dc.description.sponsorshipThis study was supported by the Trakya University Scientific Research Fund (TUBAP 2018/197).en_US
dc.identifier.doi10.1016/j.tiv.2021.105191
dc.identifier.issn0887-2333
dc.identifier.issn1879-3177
dc.identifier.pmid33962019en_US
dc.identifier.scopus2-s2.0-85108083843en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.tiv.2021.105191
dc.identifier.urihttps://hdl.handle.net/20.500.14551/20456
dc.identifier.volume75en_US
dc.identifier.wosWOS:000672807200014en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofToxicology In Vitroen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectDiabetic Macular Edemaen_US
dc.subjectMelatoninen_US
dc.subjectMitochondrial Fissionen_US
dc.subjectMitophagyen_US
dc.subjectBiogenesisen_US
dc.subjectBlood-Retinal Barrieren_US
dc.subjectEndothelial Growth-Factoren_US
dc.subjectCell-Deathen_US
dc.subjectPathogenesisen_US
dc.subjectRetinopathyen_US
dc.subjectBiogenesisen_US
dc.subjectMitophagyen_US
dc.subjectFissionen_US
dc.subjectStressen_US
dc.subjectFusionen_US
dc.subjectOxygenen_US
dc.titleMelatonin prevents blood-retinal barrier breakdown and mitochondrial dysfunction in high glucose and hypoxia-induced in vitro diabetic macular edema modelen_US
dc.typeArticleen_US

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