Essential role of growth hormone in ischemia-induced retinal neovascularization.
Retinal neovascularization is the major cause of untreatable blindness. The role of growth hormone (GH) in ischemia-associated retinal neovascularization was studied in transgenic mice expressing a GH antagonist gene and in normal mice given an inhibitor of GH secretion (MK678). Retinal neovascularization was inhibited in these mice in inverse proportion to serum levels of GH and a downstream effector, insulin-like growth factor-I (IGF-I). Inhibition was reversed with exogenous IGF-I administration. GH inhibition did not diminish hypoxia-stimulated retinal vascular endothelial growth factor (VEGF) or VEGF receptor expression. These data suggest that systemic inhibition of GH or IGF-I, or both, may have therapeutic potential in preventing some forms of retinopathy.
Smith
L E
LE
Department of Ophthalmology, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA. smith_lo@a1.tch.harvard.edu
Kopchick
J J
JJ
Chen
W
W
Knapp
J
J
Kinose
F
F
Daley
D
D
Foley
E
E
Smith
R G
RG
Schaeffer
J M
JM
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007511:Ischemia; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010456:Peptides, Cyclic / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015861:Retinal Neovascularization / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006727:Hormone Antagonists; D008222:Lymphokines; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C040968:seglitide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone