{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:09:06Z","timestamp":1792188546649,"version":"4.4.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006360","name":"Bundesministerium f\u00fcr Wirtschaft und Energie","doi-asserted-by":"publisher","award":["ZF4603201AW8"],"award-info":[{"award-number":["ZF4603201AW8"]}],"id":[{"id":"10.13039\/501100006360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec022\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Glaucoma, a leading cause of blindness, is often driven by elevated intraocular pressure (IOP), which damages the optic nerve. Transscleral filtration surgery reduces IOP but is frequently complicated by excessive wound healing from Tenon fibroblasts (TFs), impeding aqueous humor absorption. Mitomycin C (MMC), used for over 30 years in ophthalmic surgeries, inhibits TF proliferation but carries significant side effects, including hypotony, blebitis, and endophthalmitis, due to its non-selective cytotoxicity. MMC\u2019s inability to entirely prevent fibrosis increases surgical failure risk, often necessitating further interventions like bleb needling. This study investigates whether ascorbic acid (AA) and hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) can selectively target TFs without damaging scleral fibroblasts (SFs)\n                      <jats:italic>in vitro<\/jats:italic>\n                      , using MMC as a benchmark.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec023\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary human TFs and SFs were cultured from patient trabeculectomy tissues. Cells were treated with various concentrations of MMC, AA, or H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . Cytotoxic effects were analyzed via live-cell imaging. Immunocytochemistry and Western Blot assessed catalase expression in both cell types and recombinant catalase was used to validate its protective effect against AA- and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      -induced cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec024\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Short-term exposure (5\u2009min) to 0.02%\u20130.04% MMC or long-term exposure to 0.00025%\u20130.001% MMC caused cytotoxicity in TFs and SFs, with SFs dying significantly earlier. In contrast, AA (6\u20138\u2009mM) selectively induced cell death in TFs without harming SFs. H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      also showed selective cytotoxicity towards TFs. Lower catalase expression in TFs compared to SFs was determined via Western blot and immunocytochemistry, highlighting a mechanism for this selective effect. Recombinant catalase neutralized the cytotoxic effects of AA and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      on TFs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec025\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Unlike MMC, Ascorbic acid and hydrogen peroxide exhibit selective cytotoxicity towards Tenon fibroblasts, which may provide a safer, more targeted approach for preventing fibrosis in glaucoma surgery. Additional\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies are needed to explore the clinical applicability of these findings.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0320558","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T19:17:57Z","timestamp":1743621477000},"page":"e0320558","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Selective toxicity of ascorbic acid and hydrogen peroxide on human tenon cells without harming scleral cells in vitro: A possible alternative to non-selective mitomycin C?"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-4084","authenticated-orcid":true,"given":"Heiko","family":"Fuchs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Meister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin C.","family":"Bartram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Pielen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Junker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Framme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"issue":"3","key":"pone.0320558.ref001","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1089\/jop.1990.6.175","article-title":"Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma","volume":"6","author":"CW Chen","year":"1990","journal-title":"J Ocul Pharmacol"},{"issue":"9","key":"pone.0320558.ref002","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/S0161-6420(92)31781-6","article-title":"Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon\u2019s capsule fibroblasts","volume":"99","author":"HD Jampel","year":"1992","journal-title":"Ophthalmology"},{"issue":"1","key":"pone.0320558.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3341\/kjo.1999.13.1.7","article-title":"Mitomycin C-induced apoptosis in cultured human Tenon\u2019s capsule fibroblasts","volume":"13","author":"JW Kim","year":"1999","journal-title":"Korean J Ophthalmol"},{"issue":"10","key":"pone.0320558.ref004","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S0161-6420(95)30829-9","article-title":"Scleritis after glaucoma filtering surgery with mitomycin C","volume":"102","author":"S Fourman","year":"1995","journal-title":"Ophthalmology"},{"issue":"5","key":"pone.0320558.ref005","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/aos.12257","article-title":"Endophthalmitis and severe blebitis following trabeculectomy. 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