title: Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice.
abstract: OBJECTIVE
  To examine the ability and mechanism of the 16 kDa N-terminal fragment of human prolactin (16K hPRL) in the inhibition of abnormal retinal neovascularization.
  
  
  METHODS
  The 16K hPRL-encoding sequence was inserted into an adenoviral vector (16K-Ad). Western blot analysis verified the expression of 16K hPRL and inhibition of proliferation, confirming functional activity of the 16K hPRL in virus-infected adult bovine aortic endothelial (ABAE) cells. 16K hPRL inhibited retinal neovascularization in a mouse model of oxygen-induced retinopathy. The ability of recombinant 16K hPRL expressed in E. coli (r16K hPRL) was compared to that of endostatin in inducing apoptosis of cultured human retinal endothelial cells (HREC).
  
  
  RESULTS
  16K was expressed in virus-infected ABAE cells and resulted in a dose-dependent inhibition of cell proliferation. Eyes injected with 16K-Ad showed a reduction in preretinal neovascularization of 82.3 +/- 9.3% (P < 0.00001) when compared to uninjected controls. r16K hPRL was 100 times more potent than endostatin in inducing apoptosis in HRECs.
  
  
  CONCLUSIONS
  Intravitreal administration of 16K hPRL inhibited neovascularization in the mouse model of oxygen-induced retinopathy. 16K hPRL stimulated apoptosis in HRECs and inhibited cell proliferation in ABAE cells. These results suggested a potential therapeutic role for 16K hPRL in the treatment of proliferative retinopathies.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Ngoc-Quynh-Nhu
authors.initials: NQ
authors.lastname: Nguyen
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Frauke
authors.initials: F
authors.lastname: Bentzien
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Shaw
authors.forename: Francoise
authors.initials: F
authors.lastname: Rentier-Delrue
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Richard
authors.initials: R
authors.lastname: Weiner
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D043169:Endostatins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity*; D010446:Peptide Fragments / Q000235:genetics / Q000627:therapeutic use*; D011247:Pregnancy; D011388:Prolactin / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012160:Retina / Q000187:drug effects*; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D011388:Prolactin; D010100:Oxygen