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Updated: Aug 3, 2026
An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
Published on: August 6, 2020
Angiostatin inhibits pathological but not physiological retinal angiogenesis
T A Drixler1, I H Borel Rinkes, E D Ritchie
1Department of Surgery, Laboratory of Medical Oncology, University Medical Center, 3508 GA Utrecht, The Netherlands.
Purpose:
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.
Insights
Angiostatin effectively inhibits pathologic retinal angiogenesis in mice without impacting normal development. This suggests antiangiogenic therapy is a promising treatment for proliferative retinopathies.
Area of Science:
- Ophthalmology
- Vascular Biology
- Developmental Biology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for development but can drive diseases.
- Antiangiogenic therapies offer a targeted approach for managing angiogenesis-dependent conditions.
- Angiostatin, a potent inhibitor of angiogenesis, has shown therapeutic potential.
Purpose of the Study:
- To evaluate the effects of angiostatin on pathologic and physiologic retinal angiogenesis.
- To assess the impact of angiostatin on the growth and development of newborn mice.
Main Methods:
- Oxygen-induced retinopathy model in mice.
- Systemic and intravitreal administration of angiostatin.
- Assessment of retinal neovascularization and normal vascularization via fluorescein angiography and endothelial cell counting.
- Monitoring of growth and organogenesis from postnatal day 0 to 14.
Main Results:
- Systemic angiostatin completely inhibited hypoxia-induced retinal neovascularization without affecting normal retinal vascularization.
- Intravitreal angiostatin reduced pathologic retinal blood vessel proliferation by 62%.
- Neither treatment method impaired overall growth or organ development in newborn mice.
Conclusions:
- Angiostatin effectively inhibits pathological retinal angiogenesis induced by oxygen exposure.
- Angiostatin does not interfere with physiological retinal vascularization or general development in neonatal mice.
- Antiangiogenic therapy with angiostatin shows promise for treating proliferative retinopathies.
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