title: Palpebral conjunctival transient amplifying cells originate at the mucocutaneous junction and their progeny migrate toward the fornix.
abstract: OBJECTIVE
  The conjunctival epithelium performs an important role in the homeostasis and integrity of the eye. These cells need to be replaced in order to protect the integrity of the ocular surface. Epithelial cells are replaced from slow cycling stem cells which in turn produce transient amplifying cells that undergo further divisions before becoming mature conjunctival epithelial cells. The natural history of the bulbar palpebral conjunctival cells has not been previously described.
  
  
  METHODS
  A single injection of bromodeoxyuridine (brdU), a thymidine analogue, was administered intraperitoneally to adult rabbits at a concentration of 50 mg/kg body weight. The rabbits were sacrificed at 1, 3, 5, and 7 days following the injections. The orbital contents including the eyelids were exenerated en bloc, frozen in a manner that maintained the orientation and continuity between the eyelids and globe and sectioned in a parasagittal plane. The tissue was stained immunohistochemically to detect brdU labeled conjunctival epithelial cells. The brdU-positive epithelial cells were counted in a series of 0.4 mm zones starting at the mucocutaneous junction of the eyelid and progressing through the fornix and bulbar conjunctiva. Rabbit eyelids and human eyelid surgical specimens were stained for cyclin D1, a marker for cells that are in the G1 phase of the cell cycle.
  
  
  RESULTS
  In both the upper and lower eyelids, the peak number of brdU labeled cells/0.4 mm zone was located at progressively greater distances from the mucocutaneous junction in the animals sacrificed at 1, 3 and 5 days respectively, and gone by 7 days. A focus of brdU-labeled conjunctival cells remained within 1-2 mm of the mucocutaneous junction at all post-injection intervals. Foci of cyclin 1-positive cells were found almost exclusively near the mucocutaneous junction, but not in the fornix.
  
  
  CONCLUSIONS
  The mucocutaneous junction of the conjunctival epithelium is a source of actively dividing transient amplifying cells that migrate toward the fornix at a rate of about 1.7 mm/day as replacement conjunctiva so that at least some conjunctival epithelial stem cells must be located near the mucocutaneous junction. The presence of cyclin D1 staining cells at the mucocutaneous junction supports this view. These results are not necessarily at variance with previous studies, but they do diminish the relative importance assigned the forniceal region in palpabral conjunctival homeostasis. Moreover, the mucocutaneous junction might provide a therapeutically significant source of replacement conjunctival cells. The transit time of conjunctival epithelial cells is about 6 days.
authors.affiliation: Department of Ophthalmology, University of Minnesota School of Medicine, Minneapolis, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wirtschafter
authors.forename: L K
authors.initials: LK
authors.lastname: McLoon
authors.forename: J M
authors.initials: JM
authors.lastname: Ketcham
authors.forename: R J
authors.initials: RJ
authors.lastname: Weinstock
authors.forename: J C
authors.initials: JC
authors.lastname: Cheung
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D003228:Conjunctiva / Q000166:cytology* / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005143:Eyelids / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D009092:Mucous Membrane / Q000166:cytology / Q000502:physiology; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D019938:Cyclin D1; D004247:DNA; D001973:Bromodeoxyuridine