Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice.
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.
Pan
Hao
H
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, USA.
Nguyen
Ngoc-Quynh-Nhu
NQ
Yoshida
Hiroshi
H
Bentzien
Frauke
F
Shaw
Lynn C
LC
Rentier-Delrue
Francoise
F
Martial
Joseph A
JA
Weiner
Richard
R
Struman
Ingrid
I
Grant
Maria B
MB
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*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D011388:Prolactin; D010100:Oxygen