{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T18:25:02Z","timestamp":1769970302322,"version":"3.49.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["17857"],"award-info":[{"award-number":["17857"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["20914"],"award-info":[{"award-number":["20914"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The use of honey as an eye treatment encounters challenges due to its high osmolarity, low pH, and difficulties in sterilization. This study addresses these issues by employing a low concentration of honey, focusing on both <jats:italic>in-vitro<\/jats:italic> experiments and clinical trials for treating dry eye disease in corneal cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the <jats:italic>in-vitro<\/jats:italic> experiment, we investigated the impact of a 1% honey-supplemented medium (HSM) on limbal stem cells (LSCs) and keratocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and real-time polymerase chain reaction (PCR) for BCL-2, BAX, and IL-1\u03b2 gene expression. Simultaneously, in the clinical trial, 80 participants were divided into two groups, receiving either a 1% w\/v honey ophthalmic formulation or a placebo for 3\u2009months. Study outcomes included subjective improvement in dry eye symptoms, tear break-up time (TBUT), and Schirmer\u2019s test results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MTT results indicated that 1% HSM did not compromise the survival of corneal cells and significantly reduced the expression of the IL-1\u03b2 gene. Additionally, participants in the honey group demonstrated a higher rate of improvement in dry eye symptoms and a significant enhancement in TBUT values at the three-month follow-up. However, there was no significant difference between the study groups in terms of Schirmer\u2019s test values. No adverse events were observed or reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, 1% honey exhibits anti-inflammatory and anti-infective properties, proving effective in ameliorating dry eye symptoms and enhancing tear film stability in patients with dry eye disease.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration<\/jats:bold>: <jats:ext-link>https:\/\/irct.behdasht.gov.ir\/trial\/63800<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1359463","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T04:28:55Z","timestamp":1716179335000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of low dose honey on the apoptosis and inflammation gene expression in corneal limbal stem cells and keratocytes and its efficacy as an ophthalmic formulation in the treatment of dry eye: in-vitro and clinical 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