title: [Proliferative regulation in the cornea and lens].
abstract: OBJECTIVE
  To examine the mechanism of regulation of proliferation in epithelial scraped cornea and the developing lens.
  
  
  RESULTS
  C57B16 mouse, p27 (KIP 1)-/- mice, Skp2-/- mice and Skp2-/-/p27 (KIP 1)-/- double knockout mice were examined by immunocytochemistry using anti-p27 (KIP1) antibody, and cells in the "S" phase of DNA synthesis were analyzed by immunocytochemistry using anti-BrdU antibody. The p 27 (KIP 1) was expressed in basal cells of the central and peripheral region of the cornea and limbus. This expression was not detected 24 hr after epithelial scraping, when there were many cells in the "S" phase of DNA synthesis in the corneal epithelium. There was no obvious difference in the thickness and anti-BrdU staining in the corneal epithelium of p 27(KIP 1)-/- mice from that of controls. 24 hr after the epithelial scraping in the Skp 2-/- mice, the corneal epithelium was thinner than in wild-type mice and had many p 27(KIP 1) positive cells and few BrdU positive cells. In contrast, 24 hr after the epithelial scraping in the Skp 2-/-/p 27(KIP 1)-/- double knockout mice, the corneal epithelium was as thick as in wild-type mice and had many BrdU positive cells.
  
  
  CONCLUSIONS
  These results suggest that degradation of p27(KIP1) by Skp 2 is involved in the regulation of proliferation in response to wounding of the corneal epithelium. To examine the involvement of the c-maf gene in the proliferation of the lens cells, eyes of the E13 and E18 stages of wild-type and c-maf-/- mice were analyzed by BrdU incorporation assay, TUNEL assay, and immunocytochemistry using an anti-P 27 (KIP 1) and an anti-P 57 (KIP 2) antibody. In the E 13 and E 18 c-maf mutant lens, BrdU-positive cells were detected at the posterior region of the lens. Cell-cycle inhibitor P 27 (KIP 1) and P 57 (KIP 2) were expressed in the equatorial and posterior region of the lens of both wild-type and c-maf-/- lenses. These results suggest that the expression of c-maf is required for differentiation and cell cycle arrest of lens cells independent of p 27 (KIP 1) and p 57 (KIP 2).
authors.affiliation: Department of Ophthalmology, Hokkaido University School of Medicine, N 15, W 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
authors.forename: Chikako
authors.initials: C
authors.lastname: Harada
authors.forename: Satoru
authors.initials: S
authors.lastname: Kase
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakai
authors.forename: Shinzo
authors.initials: S
authors.lastname: Nishi
authors.forename: Junko
authors.initials: J
authors.lastname: Imaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nagahama
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D003315:Cornea / Q000166:cytology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D007908:Lens, Crystalline / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27