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Alexei Lukashev, Khristo Takhchidi, Natalia Gavrilova, Olga Tischenko, Alexander Revischin, Paul Tornambe; Comparison of Angiostatic Effect of Human Pigmented Epithelium Derived Factor(PEDF) and Avastin in a Neovascularization Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4878.
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A number of retinal pathologies are due to increased angiogenesis caused by imbalance between proangiogenic factors such as VEGF-A and angiostatic, for example PEDF. Avastin, a humanized mouse monoclonal antibody inhibits angiogenesis by blocking VEGF-A. Avastin and PEDF were compared in the animal neovascularization model.
Four groups (4x n=11) of neonatal Wistar rats were used in the study. Three test groups were exposed to high oxygen, then to normal oxygen. Animals in test groups expressed seven times higher proliferative activity of retinal vessels compare to the forth untreated healthy control group. The first group was injected intravitreally with 500 ng PEDF in one eye(OD), the fellow eye(OS) was injected with normal saline. The second group was injected similarly with 5000 ng of Avastin. The third test group was not injected- dystrophic control. Four days after injection eyes were removed. Indirect immunofluorescence staining with biotinylated Griffonia Simplicifolia Lectin and Streptavidin Fluorescein was used to visualize retina vascular system.
An original digital image processing method was developed to estimate density of the vessels(DOV) in the central retina. In all treated animals a statistically significant reduction of DOV was found. Reduction of neovascularization was observed in the eye treated with PEDF or Avastin and in the fellow eye; the effect was significant with respect to dystrophic control eyes. In the dystrophic control group DOV was 2.41 relative units (OD, OS); in PEDF test group 1.37 (OD), 2.06 (OS); in Avastin test group 1.56(OD), 2.19(OS); in healthy control group 1.23 (OD, OS).
Injection of PEDF resulted in a strong angiostatic effect by decreasing vascularization density of the vessels. Angiostatic effect of injection of 500 ng PEDF is slightly higher than 5000 ng of Avastin. When injected with PEDF or Avastin a contralateral effect was observed between the test and the fellow eyes. As a result, both eyes exhibited improvement.
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