{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:07:10Z","timestamp":1768075630739,"version":"3.49.0"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PNRA national Italian project PNRA18_00341\u2013Concordia platform (TEARplay)","award":["RC2765943"],"award-info":[{"award-number":["RC2765943"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RC2765943"],"award-info":[{"award-number":["RC2765943"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Corroborating data sustain the pleiotropic effect of nerve growth factor (NGF) in the protection of the visual system from dangerous stimuli, including ultraviolet (UV). Since UV exposure might promote ocular surface changes (conjunctival inflammation and matrix rearrangement), as previously reported from in vivo studies sustaining some protective NGF effects, in vitro cultures of human conjunctival fibroblasts (FBs) were developed and exposed to a single UV exposure over 15 min (0.277 W\/m2), either alone or supplemented with NGF (1\u201310\u2013100 ng\/mL). Conditioned media and cell monolayers were collected and analyzed for protein release (ELISA, ELLA microfluidic) and transcript expression (real-time PCR). A specific \u201cinflammatory to remodeling\u201d pattern (IL8, VEGF, IL33, OPN, and CYR61) as well as a few epigenetic transcripts (known as modulator of cell differentiation and matrix-remodeling (DNMT3a, HDAC1, NRF2 and KEAP1)) were investigated in parallel. UV-exposed FBs (i), showed no proliferation or significant cytoskeleton rearrangement; (ii), displayed a trkANGFR\/p75NTR phenotype; and (iii), synthesized\/released IL8, VEGF-A, IL33, OPN, and CYR61, as compared to unexposed ones. NGF addition counteracted IL8, IL33, OPN, and CYR61 protein release merely at lower NGF concentrations but not VEGF. NGF supplementation did not affect DNMT3a or HDAC1 transcripts, while it significantly upregulated NRF2 at lowest NGF doses and did not change KEAP1 expression. Taken together, a single UV exposure activated conjunctival FBs to release pro-inflammatory\/fibrogenic factors in association with epigenetic changes. The effects were selectively counteracted by NGF supplementation in a dose-dependent fashion, most probably accountable to the trkANGFR\/p75NTR phenotype. Further in vitro studies are underway to better understand this additional NGF pleiotropic effect. Since UV-shield impairments represent a worldwide alert and UV radiation can slowly affect ocular surface homeostasis (photo-ageing, cataract) or might exacerbate ocular diseases with a preexisting fibrosis (pterygium, VKC), these findings on NGF modulation of UV-exposed FBs might provide additional information for protecting the ocular surface (homeostasis) from low-grade long-lasting UV insults.<\/jats:p>","DOI":"10.3390\/ijms23116337","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T10:08:24Z","timestamp":1654510104000},"page":"6337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts"],"prefix":"10.3390","volume":"23","author":[{"given":"Graziana","family":"Esposito","sequence":"first","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-1647","authenticated-orcid":false,"given":"Bijorn Omar","family":"Balzamino","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Rocco","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and Neurobiology, CNR, 00143 Rome, Italy"},{"name":"Fondazione IRET, 40064 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Aloe","sequence":"additional","affiliation":[{"name":"Fondazione IRET, 40064 Bologna, Italy"},{"name":"Associazione NGF ONLUS, 00172 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 Science, IRCCS\u2014Fondazione Bietti, 00198 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wolffsohn, J.S., Dhallu, S., Aujla, M., Laughton, D., Tempany, K., Powell, D., Gifford, K., Gifford, P., Wan, K., and Cho, P. 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