Prevention of Ischemia-Induced Retinopathy by the Natural Ocular Antiangiogenic Agent Pigment Epithelium-Derived Factor

Aberrant blood vessel growth in the retina that underlies the pathology of proliferative diabetic retinopathy and retinopathy of prematurity is the result of the ischemia-driven disruption of the normally antiangiogenic environment of the retina. In this study, we show that a potent inhibitor of ang...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (5), p.2593-2597
Main Authors: Stellmach, Veronica, Crawford, Susan E., Zhou, Wei, Bouck, Noël
Format: Article
Language:English
Subjects:
Angiogenesis
Angiogenesis Inhibitors - pharmacology
Animals
Apoptosis
Biological Sciences
Blood vessels
Cells, Cultured
Diabetic retinopathy
Diabetic Retinopathy - etiology
Diabetic Retinopathy - prevention & control
Disease Models, Animal
Endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Eye Proteins
Eyes
Female
Humans
Hyperoxia
Ischemia - complications
Medical research
Mice
Mice, Inbred C57BL
Nerve Growth Factors
Oxygen
Proteins - pharmacology
Recombinant Proteins - pharmacology
Retina
Retinal pigments
Retinal Vessels - drug effects
Serpins - pharmacology
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Summary:Aberrant blood vessel growth in the retina that underlies the pathology of proliferative diabetic retinopathy and retinopathy of prematurity is the result of the ischemia-driven disruption of the normally antiangiogenic environment of the retina. In this study, we show that a potent inhibitor of angiogenesis found naturally in the normal eye, pigment epithelium-derived growth factor (PEDF), inhibits such aberrant blood vessel growth in a murine model of ischemia-induced retinopathy. Inhibition was proportional to dose and systemic delivery of recombinant protein at daily doses as low as 2.2 mg/kg could prevent aberrant endothelial cells from crossing the inner limiting membrane. PEDF appeared to inhibit angiogenesis by causing apoptosis of activated endothelial cells, because it induced apoptosis in cultured endothelial cells and an 8-fold increase in apoptotic endothelial cells could be detected in situ when the ischemic retinas of PEDF-treated animals were compared with vehicle-treated controls. The ability of low doses of PEDF to curtail aberrant growth of ocular endothelial cells without overt harm to retinal morphology suggests that this natural protein may be beneficial in the treatment of a variety of retinal vasculopathies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.031252398