title: Role of connective tissue growth factor in the retinal vasculature during development and ischemia.
abstract: OBJECTIVE
  To investigate the function of connective tissue growth factor (CTGF), a matricellular protein of the CCN (Cyr61/CTGF/Nov) family, in retinal vasculature during development and ischemia.
  
  
  METHODS
  CTGF expression was determined using RT-PCR, immunohistochemistry, and transgenic mice carrying CTGF promoter-driven-GFP. CTGF antibody was intraocularly injected into neonates at postnatal day (P)2, and its effect on retinal angiogenesis was analyzed at P4. Transgenic animals expressing GFP regulated by the glial fibrillary acidic protein promoter were used for astrocyte visualization. Retinal vascular occlusion was introduced by rose Bengal and laser photocoagulation on chimeric mice that were reconstituted with GFP+ bone marrow cells. Vascular repair in response to VEGF-A and CTGF was analyzed.
  
  
  RESULTS
  A temporal increase in CTGF at both mRNA and protein levels was observed in the ganglion cell layer and inner nuclear layer during development. Endothelial cells and pericytes were identified as the main cellular sources of CTGF during retinal angiogenesis. CTGF stimulated the migration of astrocytes, retinal endothelial cells, and pericytes in vitro. Inhibition of CTGF by specific antibody affected vascular filopodial extension, growth of the superficial vascular plexus, and astrocyte remodeling. In adult mice, CTGF was prominently expressed in the perivascular cells of arteries. CTGF activated bone marrow-derived perivascular cells and promoted fibrovascular membrane formation in the laser-induced adult retinopathy model.
  
  
  CONCLUSIONS
  CTGF is expressed in vascular beds and acts on multiple cell types. It is important for vessel growth during early retinal development and promotes the fibrovascular reaction in murine retinal ischemia after laser injury.
authors.affiliation: Program in Stem Cell Biology and Regenerative Medicine, University of Florida, PO Box 100201, Gainesville, FL 32610, USA. lpi@ufl.edu
authors.forename: Liya
authors.initials: L
authors.lastname: Pi
authors.forename: Huiming
authors.initials: H
authors.lastname: Xia
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Anitha K
authors.initials: AK
authors.lastname: Shenoy
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Edward W
authors.initials: EW
authors.lastname: Scott
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology; D020286:Pericytes / Q000166:cytology / Q000502:physiology; D012160:Retina / Q000254:growth & development / Q000502:physiology; D012164:Retinal Diseases / Q000473:pathology / Q000503:physiopathology*; D012171:Retinal Vessels / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*
chemical_list: D000906:Antibodies; C526318:CCN2 protein, mouse; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins