{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:04Z","timestamp":1760060224546,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015550","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RC2788872","RF-2021-12374301","971925"],"award-info":[{"award-number":["RC2788872","RF-2021-12374301","971925"]}],"id":[{"id":"10.13039\/501100015550","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Association Research Grant","award":["RC2788872","RF-2021-12374301","971925"],"award-info":[{"award-number":["RC2788872","RF-2021-12374301","971925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Growing evidence suggests that Reelin signals and cleavages are affected in neurodegenerative diseases, prospecting a potential role for Reelin in the pathogenesis of neurodegenerative processes occurring in insulted retinas. We sought to determine whether Reelin, A\u03b21-42, FTH1 and TAU proteins accumulate in ocular fluids of idiopathic epiretinal membrane (iERM) specimens and whether such accumulations depend on disease severity. Comparisons and correlation studies were used to verify the hypothesis of a Reelin, A\u03b21-42, TAU and FTH1 marker expressions in this vitreoretinal disease, extending the knowledge on the pathological spectrum of neurodegenerative eye diseases. Aqueous, vitreous and peeled-off ERM samples were collected from patients who had undergone vitrectomy and grouped according to disease severity. We found out that Reelin and A\u03b21-42 were expressed in ocular fluids and affected ERMs depending on disease severity. At stage 3, higher Reelin and A\u03b21-42 immunofluorescence staining was detected in ERMs, in agreement with the higher Reelin, A\u03b21-42, FTH1 and TAU transcript expressions by RT-PCR. Differential expressions of transcripts specific to A\u03b21-42, FTH1, GFAP and TAU occurred in vitreal hyalocytes and astrocytes, which selectively responded to vitreal exposure. This is the first study reporting the association between Reelin and ERM disease, highlighting the potential role of Reelin in neurodegenerating and Drusen-affected retinas. The potential association of neurodegenerative mediators with ERM would suggest that part of the neuronal damage activated at the vitreoretinal interphase might be driven by Reelin.<\/jats:p>","DOI":"10.3390\/biom15081187","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T15:34:53Z","timestamp":1755531293000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of Reelin, A\u03b21-42, Tau and FTH1 in Idiopathic Epiretinal Membranes: Exploring the Link Between Reelin and Neurodegenerative Biomarkers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-1647","authenticated-orcid":false,"given":"Bijorn","family":"Balzamino","sequence":"first","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-197X","authenticated-orcid":false,"given":"Graziana","family":"Esposito","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4099-0123","authenticated-orcid":false,"given":"Pamela","family":"Cosimi","sequence":"additional","affiliation":[{"name":"Retinal Surgery Unit, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-1140","authenticated-orcid":false,"given":"Rosanna","family":"Squitti","sequence":"additional","affiliation":[{"name":"Department of Laboratory Science, Research and Development Division, Ospedale Isola Tiberina\u2014Gemelli Isola, 00186 Rome, Italy"},{"name":"Department of Theoretical and Applied Sciences, eCampus University, 22100 Novedrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Amadoro","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), 00161 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6057-6154","authenticated-orcid":false,"given":"Valentina","family":"Latina","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), 00161 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Ripandelli","sequence":"additional","affiliation":[{"name":"Retinal Surgery Unit, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Cacciamani","sequence":"additional","affiliation":[{"name":"Retinal Surgery Unit, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-6071","authenticated-orcid":false,"given":"Alessandra","family":"Micera","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS-Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Joly-Amado, A., Kulkarni, N., and Nash, K.R. 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