title: Limbal epithelium is more resistant to 5-fluorouracil toxicity than corneal epithelium.
abstract: There is increasing evidence indicating that the limbal epithelium contains slow-cycling stem cells, whereas both limbal and corneal epithelia contain rapid-cycling transit amplifying cells. 5-Fluorouracil (5-FU), an antimetabolite used in glaucoma filtering procedures, is reported to inhibit rapid-cycling cells. After a 1-day subconjunctival (20 mg/eye) 5-FU injection followed by a 2-day rest, continuous BrdU labeling for 5 additional days (to also label slow-cycling stem cells) revealed that the limbal labeling index was not changed, whereas the corneal labeling index was markedly suppressed (p < 0.001). Following subconjunctival 5-FU treatments, peripheral and central corneal explant cultures showed a significantly higher magnitude of reduction of epithelial outgrowth size than limbal cultures (p < 0.05). Such a resistant nature of limbal epithelium to 5-FU toxicity was further confirmed by two different single-cell clonal growth assays. Taken together, these results indicate that the limbal epithelium has more slow-cycling cells than the corneal epithelium, and these cells selectively harvested by the subconjunctival 5-FU treatment can be used for future studies of their regulatory mechanism.
authors.affiliation: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida 33101, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Tseng
authors.forename: S H
authors.initials: SH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004351:Drug Resistance; D004848:Epithelium / Q000187:drug effects; D005472:Fluorouracil / Q000633:toxicity*; D016850:Limbus Corneae / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D013234:Stem Cells / Q000187:drug effects
chemical_list: D001973:Bromodeoxyuridine; D005472:Fluorouracil