File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Inhibition of RAP1 enhances corneal recovery following alkali injury

TitleInhibition of RAP1 enhances corneal recovery following alkali injury
Authors
Issue Date2015
PublisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
Citation
Investigative Ophthalmology & Visual Science, 2015, v. 56 n. 2, p. 711-721 How to Cite?
AbstractAbstract PURPOSE: 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.
Persistent Identifierhttp://hdl.handle.net/10722/216085
ISSN
2015 Impact Factor: 3.427
2015 SCImago Journal Rankings: 2.008

 

DC FieldValueLanguage
dc.contributor.authorPoon, MW-
dc.contributor.authorYan, L-
dc.contributor.authorJiang, D-
dc.contributor.authorQin, P-
dc.contributor.authorTse, HF-
dc.contributor.authorWong, IYH-
dc.contributor.authorWong, DSH-
dc.contributor.authorTergaonkar, V-
dc.contributor.authorLian, Q-
dc.date.accessioned2015-08-21T13:53:34Z-
dc.date.available2015-08-21T13:53:34Z-
dc.date.issued2015-
dc.identifier.citationInvestigative Ophthalmology & Visual Science, 2015, v. 56 n. 2, p. 711-721-
dc.identifier.issn0146-0404-
dc.identifier.urihttp://hdl.handle.net/10722/216085-
dc.description.abstractAbstract PURPOSE: 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.-
dc.languageeng-
dc.publisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org-
dc.relation.ispartofInvestigative Ophthalmology & Visual Science-
dc.titleInhibition of RAP1 enhances corneal recovery following alkali injury-
dc.typeArticle-
dc.identifier.emailPoon, MW: ilmwpoon@hku.hk-
dc.identifier.emailYan, L: ylmeng@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailWong, IYH: wongyhi@hku.hk-
dc.identifier.emailWong, DSH: shdwong@hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityWong, IYH=rp01467-
dc.identifier.authorityWong, DSH=rp00516-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1167/iovs.14-15268-
dc.identifier.pmid25574050-
dc.identifier.hkuros247310-
dc.identifier.volume56-
dc.identifier.issue2-
dc.identifier.spage711-
dc.identifier.epage721-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats