title: Inhibition of RAP1 enhances corneal recovery following alkali injury.
abstract: OBJECTIVE
  Recently, RAP1 (Telomeric Repeat Binding Factor 2, Interacting Protein [TERF2IP]) was discovered as a modulator that selectively regulates nuclear factor light chain kappa enhancer of activated B cells (NFκB) signaling. The roles of RAP1 in regulation of inflammation and angiogenesis for corneal recovery following corneal injury remain poorly understood. The effects of RAP1 deletion on corneal resurfacing and neovascularization in a corneal alkali burn mouse model were examined.
  
  
  METHODS
  Corneal defects and neovascularization were induced in vivo by infliction of an alkali burn to the cornea with 1 N sodium hydroxide solution in RAP1 knock-out (RKO) and wild-type (RWT) mice. Corneal resurfacing was evaluated using slit-lamp biomicroscopy. Neovascularization following injury was evaluated by bright view biomicroscopy and immunofluorescence staining with the endothelial marker platelet endothelial cell adhesion molecule (PECAM). The cytokine profiles of corneal tissue involved in inflammation and neovascularization following injury was compared between RKO and RWT mice. Corneal epithelial cells were isolated for classic scratch wound healing assay and further testing with lipopolysaccharide stimulation.
  
  
  RESULTS
  Resurfacing of the burned cornea was accelerated and angiogenesis was suppressed, faster recovery of corneal epithelial cells from classic scratch wound healing and superior tolerance of lipopolysaccharides challenge was observed in the RKO compared to RWT. Molecular investigation revealed that deletion of RAP1 reduced upregulation of inflammatory cytokine (IL1A), finely regulated the expression of angiogenic factor (VEGF), and antiangiogenic factor (PEDF), following injury for better corneal recovery.
  
  
  CONCLUSIONS
  Deficiency of RAP1 facilitates corneal recovery after injury. Specificity of RAP1 inhibition may lead to design of specific inhibitors of NFκB in the treatment of ocular injuries.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Ming Wai
authors.initials: MW
authors.lastname: Poon
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Limeng
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qin
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Ian Y
authors.initials: IY
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: David S H
authors.initials: DS
authors.lastname: Wong
authors.affiliation: Institute of Molecular and Cellular Biology, Biopolis, Singapore.
authors.forename: Vinay
authors.initials: V
authors.lastname: Tergaonkar
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, Hong Kong, China.
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
mesh_terms: D000468:Alkalies / Q000633:toxicity; D000818:Animals; D002057:Burns, Chemical / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D065306:Corneal Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016510:Corneal Neovascularization / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005126:Eye Burns / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D000089804:Shelterin Complex; D015398:Signal Transduction; D034501:Telomere-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D000468:Alkalies; D012333:RNA, Messenger; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins
keywords: NFκB; RAP1; angiogenesis; corneal resurfacing; corneal wound healing; cytokines