Angiostatin inhibits pathological but not physiological retinal angiogenesis.
OBJECTIVE
Antiangiogenic treatment is a promising new therapy for angiogenesis-dependent diseases. In the current study, the biologic effects on pathologic and physiological angiogenesis in the retina of angiostatin, a very potent angiogenesis inhibitor were determined. In addition, the effects of angiostatin on the growth and development of newborn mice were examined.


METHODS
Oxygen-induced retinopathy was induced by subjecting mice postnatal day (P)7 to hyperoxic conditions (5 days) followed by normoxic conditions (relative hypoxia). Mice were treated with angiostatin (intravitreal or systemic). Retinal blood vessels were visualized by fluorescein angiography. Retinal neovascularization was assessed by counting intravitreal endothelial cell nuclei. Growth and organogenesis were determined between P0 and P14.


RESULTS
Relative hypoxia resulted in intravitreal proliferation of retinal blood vessels. However, proliferation was inhibited completely by systemic administration of angiostatin without affecting normal retinal vascularization. After intravitreal injection of angiostatin, pathologic proliferation of the retinal blood vessels was impaired by 62%. Neither systemic nor intravitreal treatment impaired the development or growth of organs throughout the body.


CONCLUSIONS
Angiostatin inhibits oxygen-induced intravitreal pathologic retinal angiogenesis without affecting the development of physiological retinal vascularization, development, and growth of newborn mice. Therefore, antiangiogenic treatment may be a useful tool in the treatment of proliferative retinopathies.
Drixler
T A
TA
Department of Surgery, Laboratory of Medical Oncology, University Medical Center, 3508 GA Utrecht, The Netherlands.
Borel Rinkes
I H
IH
Ritchie
E D
ED
Treffers
F W
FW
van Vroonhoven
T J
TJ
Gebbink
M F
MF
Voest
E E
EE
D043168:Angiostatins; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology*; D012171:Retinal Vessels / Q000187:drug effects* / Q000254:growth & development
D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen