title: Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the alphaA-crystallin promoter.
abstract: OBJECTIVE
  During growth of the embryonic eye, dose- and site-specific expression of heparin-binding growth factors is critical for the formation of an appropriate vascular supply. Overexpression of vascular endothelial growth factor-A(188) (VEGF-A(188)), a strongly heparin-binding, endothelial-specific mitogen, leads to severe disturbance of vascular and overall ocular morphology. This study aimed to evaluate the effects of VEGF-A(188) overexpression on growth of ocular tissue components.
  
  
  METHODS
  Stereological and immunohistochemical methods were employed to identify the vascular profiles, ocular tissue proportions, and cell types in VEGF-A(188) transgenic mice and compare them with wild-type mice.
  
  
  RESULTS
  In VEGF-A(188) transgenic mice, both lens tissue and total ocular volume were reduced, whereas cross-sectional areas of hyaloid blood vessels, retina, iris, and optic stalk tissues were significantly increased compared to wild-type mice. Endothelial and pericyte cell numbers in the hyaloid vasculature of transgenic mice were increased three fold, with pericytes assuming their characteristic extraluminal position.
  
  
  CONCLUSIONS
  Overexpression of VEGF-A(188) in the murine lens results in microphthalmia, in addition to hypertrophy and persistence of the hyaloid vasculature. This is similar to the human disorder persistent hyperplastic primary vitreous (PHPV). The murine model is a useful, experimental paradigm for investigation of this condition.
authors.affiliation: School of Biomedical Sciences, Medical School, University of Nottingham, Nottingham, United Kingdom. catrinrutland@hotmail.com <catrinrutland@hotmail.com>
authors.forename: Catrin S
authors.initials: CS
authors.lastname: Rutland
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Mitchell
authors.forename: Muneeb
authors.initials: M
authors.lastname: Nasir
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Hannes C A
authors.initials: HC
authors.lastname: Drexler
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D000013:Congenital Abnormalities / Q000209:etiology; D003315:Cornea / Q000473:pathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D005123:Eye / Q000098:blood supply*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006965:Hyperplasia; D006984:Hypertrophy; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000209:etiology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020286:Pericytes / Q000473:pathology; D011401:Promoter Regions, Genetic; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D038202:alpha-Crystallin A Chain / Q000235:genetics
chemical_list: D000199:Actins; D000943:Antigens, Differentiation; D019812:Heparan Sulfate Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D038202:alpha-Crystallin A Chain; C036763:monocyte-macrophage differentiation antigen; C467480:vascular endothelial growth factor A, mouse