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Alexei Lukashev, Natalia Gavrilova, Irina Saburina, Vasilii Shirokov, Olga Tischenko; Comparison of Angiostatic Properties of Pigmented Epithelium Derived Factor(PEDF) and Infliximab in a Neovascularization Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2941.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze and compare the use of Infliximab alone and in combination with PEDF on retina in a neovascularization model.
A neonatal neovascularization model in Wistar rats, exposed to hyperoxic then to normal environment was used in experiments. Two blocks of experiments were performed.Block 1-Establishing a baseline: Three tests (3x N=11) and one healthy control groups were used to define the level of tumor necrotic factor (TNF-alpha) and vascular endothelial growth factor (VEGF 121,165) at day 13, 15 and 18 post natal(PN) in relation to the density of vascularization(DOV) of retina.Block 2-Angiostatic experiment: Six (6x N=11) groups were injected intravitreally on day 13-15 PN by Infleximab; PEDF and a combination of Infleximab and PEDF. Additional two groups(2x N=11) were injected with Bevacizumab and Ranibizumab for comparison. 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. The level of TNF-alpha and VEGF 121,165 in the sensory retina and retinal pigmented epithelial (RPE) cells layer were measured by ELISA.
The increase of the TNF-alpha level is significant at day 15 PN, and VEGF-165 at day 18 PN. Both trends correlate to each other(r=0.78; p<0.05) as well as with DOV (r= 0.72; 0.82; p<0.05). All test groups in the block 2 express significant decrease of DOV along with a significant decrease of TNF-alpha and VEGF165. Most notably this effect was observed in the group injected with Infliximab at day 13 PN and PEDF at day 15 PN.
Injection of Infliximab and PEDF resulted in a strong angiostatic effect by decreasing the density of vascularization. Angiostatic effect of injection of Infliximab and PEDF in combination is higher than Infleximab, PEDF, Bevacizumab, Ranibizumab just alone.
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