title: Overexpression of CDKN1B inhibits fibroblast proliferation in a rabbit model of experimental glaucoma filtration surgery.
abstract: OBJECTIVE
  To investigate the potential antiproliferative effect of cyclin-dependent kinase inhibitor 1B (CDKN1B) overexpression in a rabbit model of glaucoma filtration surgery (GFS).
  
  
  METHODS
  The recombinant adenovector expressing exogenous CDKN1B was delivered to Tenon's capsule by subconjunctival injection during unilateral filtration surgery. The time course of CDKN1B expression was monitored by immunohistochemistry and Western blot analysis. Evaluation of proliferating activity was performed by proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar organizing region (AgNOR) staining, and fibroblast-specific protein 1 (FSP-1). Cyclin-dependent kinase 2 (Cdk2) and Cdk4 expression were detected with immunohistochemical analysis.
  
  
  RESULTS
  The overexpression of CDKN1B in Tenon's capsule was monitored throughout the experimental period. Immunoreactivity to CDKN1B was mainly observed in the nucleus of fibroblasts. The increased expression of CDKN1B in sclera was detected up to 21 days after viral infection, whereas the level of CDKN1B protein in corneal stroma was not significantly increased. The overexpression of CDKN1B induced a significant decrease in AgNOR number/nucleus and area/nucleus, PCNA staining, FSP-1 positive cells, and the decreased expressions of Cdk2 and Cdk4, as evidenced by nuclear and cytoplasmic immunoreactivity to Cdk2 and Cdk4 antibodies in positive fibroblasts.
  
  
  CONCLUSIONS
  The persistent overexpression of CDKN1B mediated by the recombinant adenovector expressing exogenous CDKN1B in Tenon's fibroblasts after GFS may lead to the inhibition of fibroblast proliferation and the downregulation of Cdk2 and Cdk4 activity, thereby reducing the severity of scar formation and the surgical outcome.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital, Xi'an Medical University, Xi'an, China.
authors.forename: Jian-gang
authors.initials: JG
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.forename: Ling-xiao
authors.initials: LX
authors.lastname: Zhou
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Li
authors.forename: Peng-rui
authors.initials: PR
authors.lastname: Sun
authors.forename: Nai-xue
authors.initials: NX
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D018463:Filtering Surgery; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D011817:Rabbits
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27