{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:48:07Z","timestamp":1779889687749,"version":"3.53.1"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Carisbo, Bologna","award":["2017\/0330 to PV"],"award-info":[{"award-number":["2017\/0330 to PV"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neuroprotection represents a promising approach for mitigating retinal degeneration. Cord blood serum (CBS), rich in trophic factors such as the brain-derived neurotrophic factor (BDNF), has shown therapeutic potential for ocular surface diseases; however, its role in retinal neuroprotection remains underexplored. This study evaluates the protective effects of CBS on retinal pigment epithelium (ARPE-19) and photoreceptor-like (661W) cells exposed to oxidative stress. Cells were cultured in media supplemented with fetal bovine serum (FBS) or CBS with either high (CBS-H) or low (CBS-L) BDNF content. Oxidative stress was induced using hydrogen peroxide (H2O2), and cell viability was measured via an MTS assay. ZO-1 expression was analyzed in ARPE-19 cells to assess tight junction integrity, while mitochondrial function in 661W cells was examined using MitoRed staining. TrkB receptor involvement was investigated using the inhibitor K252a and Western blot analysis. CBS significantly improved cell viability under oxidative conditions. CBS-H increased ZO-1 expression in ARPE-19 cells, indicating preserved epithelial integrity. In 661W cells, CBS maintained mitochondrial integrity and enhanced TrkB phosphorylation, while TrkB inhibition reduced its protective effect. These findings indicate that CBS confers neuroprotection through BDNF-TrkB signaling together with other trophic factors, supporting its potential as a multifactorial therapeutic strategy for retinal degeneration that deserves further exploration.<\/jats:p>","DOI":"10.3390\/biom16010131","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective Effects of Cord Blood Serum (CBS) on Retinal Pigment Epithelium (ARPE-19) and Retinal Photoreceptor-like (661W) Cell Line Viability Under In Vitro Oxidative Stress"],"prefix":"10.3390","volume":"16","author":[{"given":"Ilenia","family":"Motta","sequence":"first","affiliation":[{"name":"Alma Mater Institute on Healthy Planet, Alma Mater Studiorum University of Bologna, Via Massarenti 11, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-7583","authenticated-orcid":false,"given":"Ilaria","family":"Piano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4157-111X","authenticated-orcid":false,"given":"Silvia","family":"Bisti","sequence":"additional","affiliation":[{"name":"National Institute of Biostructure and Biosystem (INBB), V.le Medaglie D\u2019Oro 305, 00136 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bergantin","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-5886","authenticated-orcid":false,"given":"Marina","family":"Buzzi","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia","family":"Gargini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2951-5337","authenticated-orcid":false,"given":"Piera","family":"Versura","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy"},{"name":"Ophtalmology Unit, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Via Palagi 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1054\/jocn.2001.1027","article-title":"Neuroprotection and neurodegenerative disease","volume":"9","author":"Vajda","year":"2002","journal-title":"J. Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.pneurobio.2010.06.009","article-title":"Microglia and neuroprotection: From in vitro studies to therapeutic applications","volume":"92","author":"Palazzi","year":"2010","journal-title":"Prog. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev-vision-102016-061422","article-title":"Neuroprotection in Glaucoma: Animal Models and Clinical Trials","volume":"3","author":"Almasieh","year":"2017","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_4","first-page":"246","article-title":"Neuroprotection in Optic Neuropathy","volume":"7","author":"Levin","year":"2018","journal-title":"Asia-Pac. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1089\/ars.2017.7144","article-title":"Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation","volume":"29","author":"Paloczi","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1017\/cjn.2021.223","article-title":"Neuroprotection in Acute Ischemic Stroke: A Brief Review","volume":"49","author":"Buchan","year":"2022","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_7","first-page":"73","article-title":"Neurodegeneration and Neuroprotection in Glaucoma","volume":"89","author":"Gauthier","year":"2016","journal-title":"Yale J. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1089\/jop.2017.0041","article-title":"Targets of Neuroprotection in Glaucoma","volume":"34","author":"He","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1111\/bph.15386","article-title":"Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis","volume":"178","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mahmud, N.M., Paraoan, L., Khaliddin, N., and Kamalden, T.A. (2022). Thymoquinone in Ocular Neurodegeneration: Modulation of Pathological Mechanisms via Multiple Pathways. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.786926"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Patel, C., Pande, S., Sagathia, V., Ranch, K., Beladiya, J., Boddu, S.H.S., Jacob, S., Al-Tabakha, M.M., Hassan, N., and Shahwan, M. (2023). Nanocarriers for the Delivery of Neuroprotective Agents in the Treatment of Ocular Neurodegenerative Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030837"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Samarkanova, D., Cox, S., Hernandez, D., Rodriguez, L., Casaroli-Marano, R.P., Madrigal, A., and Querol, S. (2020). Cord Blood Platelet Rich Plasma Derivatives for Clinical Applications in Non-transfusion Medicine. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00942"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.51329\/mehdiophthal1463","article-title":"Safety and efficacy of eye drops from umbilical cord blood platelet lysate to treat resistant corneal ulcer","volume":"11","author":"Dawood","year":"2023","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12014-024-09524-2","article-title":"Cord blood platelet-rich plasma: Proteomics analysis for ophthalmic applications","volume":"22","author":"Savastano","year":"2025","journal-title":"Clin. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.transci.2017.07.023","article-title":"Blood derived eye drops for the treatment of cornea and ocular surface diseases","volume":"56","author":"Giannaccare","year":"2017","journal-title":"Transfus. Apher. Sci."},{"key":"ref_16","first-page":"s44","article-title":"Cord blood serum-based eye drops: The impact of donor haematological and obstetric factors on the variability of epidermal growth factor levels","volume":"12","author":"Versura","year":"2014","journal-title":"Blood Transfus."},{"key":"ref_17","first-page":"145","article-title":"Targeting growth factor supply in keratopathy treatment: Comparison between maternal peripheral blood and cord blood as sources for the preparation of topical eye drops","volume":"14","author":"Versura","year":"2016","journal-title":"Blood Transfus."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/ICO.0000000000001257","article-title":"Efficacy of 2-Month Treatment with Cord Blood Serum Eye Drops in Ocular Surface Disease: An In Vivo Confocal Microscopy Study","volume":"36","author":"Giannaccare","year":"2017","journal-title":"Cornea"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Di Marco, S., Riccitelli, S., Di Paolo, M., Campos, E., Buzzi, M., Bisti, S., and Versura, P. (2020). Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced Neurodegeneration in Albino Rat Retinas. Biomolecules, 10.","DOI":"10.3390\/biom10050678"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ciavarella, C., Buzzi, M., Bergantin, E., Di Marco, S., Giannaccare, G., Campos, E., Bisti, S., and Versura, P. (2020). Effects of Cord Blood Serum (CBS) on viability of retinal M\u00fcller glial cells under in vitro injury. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234145"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Valente, S., Ciavarella, C., Astolfi, G., Bergantin, E., Curti, N., Buzzi, M., Fontana, L., and Versura, P. (2022). Impact of Freeze-Drying on Cord Blood (CB), Serum (S), and Platelet-Rich Plasma (CB-PRP) Preparations on Growth Factor Content and In Vitro Cell Wound Healing. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810701"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Si, Z., Zheng, Y., and Zhao, J. (2023). The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy. Biomolecules, 13.","DOI":"10.3390\/biom13060901"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.exer.2014.01.010","article-title":"Understanding photoreceptor outer segment phagocytosis: Use and utility of RPE cells in culture","volume":"126","author":"Mazzoni","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1152\/physiol.00038.2009","article-title":"Phagocytosis of retinal rod and cone photoreceptors","volume":"25","author":"Kevany","year":"2010","journal-title":"Physiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1167\/iovs.03-1114","article-title":"Expression of Cone-Photoreceptor\u2013Specific Antigens in a Cell Line Derived from Retinal Tumors in Transgenic Mice","volume":"45","author":"Tan","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00109-017-1506-8","article-title":"Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, \u03b1CT1, reduces VEGF-dependent RPE pathophysiology","volume":"95","author":"Obert","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1021\/acschemneuro.2c00582","article-title":"Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration","volume":"13","author":"Corsi","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u08a4\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Domenici, L., Origlia, N., Falsini, B., Cerri, E., Barloscio, D., Fabiani, C., Sans\u00f2, M., and Giovannini, L. (2014). Rescue of retinal function by BDNF in a mouse model of glaucoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115579"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lambuk, L., Mohd Lazaldin, M.A., Ahmad, S., Iezhitsa, I., Agarwal, R., Uskokovi\u0107, V., and Mohamud, R. (2022). Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.875662"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.2147\/DDDT.S251941","article-title":"Effect of Platelet-Activating Factor on Barrier Function of ARPE-19 Cells","volume":"14","author":"Zhang","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Perez-Estrada, J.R., Tangeman, J.A., Proto-Newton, M., Sanaka, H., Smucker, B., and Del Rio-Tsonis, K. (2023). Distinct Metabolic States Direct Retinal Pigment Epithelium Cell Fate Decisions. bioRxiv.","DOI":"10.1101\/2023.09.26.559631"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19838","DOI":"10.1021\/acs.jafc.4c04394","article-title":"Ginsenoside Re Prevents Depression-like Behaviors via Inhibition of Inflammation, Oxidative Stress, and Activating BDNF\/TrkB\/ERK\/CREB Signaling: An In Vivo and In Vitro Study","volume":"72","author":"Chen","year":"2024","journal-title":"J. Agric. Food Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/131\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T11:14:45Z","timestamp":1768216485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/1\/131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biom16010131"],"URL":"https:\/\/doi.org\/10.3390\/biom16010131","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}