title: VEGF mRNA and protein concentrations in the developing human eye.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF), a well-characterized regulator of angiogenesis, has been mechanistically implicated in retinal neovascularization and in the pathogenesis of retinopathy of prematurity. However, the ontogeny of VEGF expression in the human fetal retina is not well known. Because retinal vasculature grows with gestational maturation, we hypothesized that VEGF expression also increases in the midgestation human fetal eye as a function of gestational age.
  
  
  METHODS
  To identify changes in VEGF gene expression during normal human development, we measured VEGF mRNA by quantitative PCR and measured VEGF protein by enzyme-linked immunosorbent assay and western blots in 10-24 wk gestation fetal vitreous, retina, and serum.
  
  
  RESULTS
  VEGF mRNA expression in the retina increased with gestational age. VEGF isoform A, particularly its VEGF121 splice variant, contributed to this positive correlation. Consistent with these findings, we detected increasing VEGF121 protein concentrations in vitreous humor from fetuses of 10-24 wk gestation, while VEGF concentrations decreased in fetal serum.
  
  
  CONCLUSIONS
  VEGF121 mRNA and protein concentrations increase with increasing gestational age in the developing human retina. We speculate that VEGF plays an important role in normal retinal vascular development, and that preterm delivery affects production of this vascular growth factor.
authors.affiliation: Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: Irene T
authors.initials: IT
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Suzanne
authors.initials: S
authors.lastname: McConaghy
authors.affiliation: Center for Neonatal and Pediatric Gastrointestinal Disease, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Kopperuncholan
authors.initials: K
authors.lastname: Namachivayam
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Halloran
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Kurundkar
authors.affiliation: Center for Neonatal and Pediatric Gastrointestinal Disease, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Krishnan
authors.initials: K
authors.lastname: MohanKumar
authors.affiliation: 1] Center for Neonatal and Pediatric Gastrointestinal Disease, University of Illinois at Chicago, Chicago, Illinois [2] Division of Neonatology, Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Akhil
authors.identifier: 0000000315027663
authors.initials: A
authors.lastname: Maheshwari
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Ohls
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D012333:RNA, Messenger / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D015861:Retinal Neovascularization; D012178:Retinopathy of Prematurity / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014822:Vitreous Body / Q000196:embryology*
chemical_list: D000199:Actins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases