{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T22:26:31Z","timestamp":1793571991270,"version":"4.5.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>5-Fluorouracil (5-FU) is a commonly used antimetabolite in cancer therapy. Patients (25% to 38%) undergoing chronic systemic 5-FU chemotherapy are affected by ocular toxicity and require cessation of therapy to manage ocular complications. However, the mechanism by which 5-FU crosses the blood-tear barrier is not well understood. The current study investigates the role of organic anion transporters (OAT2 and 3) in the blood-tear barrier of the lacrimal gland, in trafficking 5-FU into the ocular surface.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>\n                      Computer simulations were performed to determine the substrate specificity of 5-FU for OAT isoforms. Tear pharmacokinetic studies of intravenous 5-FU were conducted in rabbits (\n                      <jats:italic toggle=\"yes\">n = 3<\/jats:italic>\n                      per group), with and without OAT blockade. The ocular adverse effect of 5-FU was assessed\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      using human corneal epithelial cells (HCEC). Furthermore, the potential of artificial tears to reduce ocular accumulation of 5-FU was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Computational studies indicated that 5-FU is a substrate for OAT2. 5-FU was detected in the tear from systemic circulation (C\n                      <jats:sub>max<\/jats:sub>\n                      = 16.7 \u00b5g\/mL) within five minutes of administration. The concentration of 5-FU reaching the ocular surface reduced HCEC viability in a concentration-dependent manner. Furthermore, topical pretreatment with OAT2 blockers reduced 5-FU exposure in tears by 1.53 to 2.96-fold, and prophylactic artificial tears containing polyethylene glycol 400 and propylene glycol achieved a 1.68-fold reduction in 5-FU exposure in tears.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Blocking OAT-2 with eye drops (OAT2 blockers and artificial tears) reduced the tear concentration of 5-FU, suggesting a potential to minimize ocular toxicity of 5-FU in patients undergoing chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261467574","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:54:21Z","timestamp":1784008461000},"page":"687-695","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ocular Toxicity of Systemic 5-Fluorouracil Chemotherapy: Role of Lacrimal Gland Transporters"],"prefix":"10.1177","volume":"42","author":[{"given":"Manthan S.","family":"Hiremath","sequence":"first","affiliation":[{"name":"Translational Pharmaceutics Research Laboratory (TPRL), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounika","family":"Varkala","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutics Research Laboratory (TPRL), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Malani","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutics Research Laboratory (TPRL), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Singh","sequence":"additional","affiliation":[{"name":"Hariram Motumal Nasta &amp; Renu Hariram Nasta Ophthalmic Plastic Surgery Services, KAR Campus, LV Prasad Eye Institute, Hyderabad, India."},{"name":"Prof. Krothapalli Ravindranath Ophthalmic Research Biorepository, LV Prasad Eye Institute, Hyderabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7864-6053","authenticated-orcid":false,"given":"Jayabalan","family":"Nirmal","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutics Research Laboratory (TPRL), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, India."},{"name":"Centre for Ocular Drug Delivery Devices (CODD), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.6-suppl_4-3"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules13081551"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh264"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-021-01441-2"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1188\/18.CJON.627-634"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.1994.11741178"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-021-13969-5"},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.IOP.0000066648.33513.3D"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-8258(90)90127-7"},{"issue":"6","key":"e_1_3_5_12_1","first-page":"438","article-title":"Lacrimal duct stenosis and other ocular toxicity associated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy for early stage breast cancer","volume":"13","author":"Stevens A","year":"2001","unstructured":"11.Stevens A, , Spooner D. 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