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Y. Miura, A. Klettner, J. Roider; Bevacizumab (Avastin) and Ranibizumab (Lucentis) Enhance the Permeability of Cultured Retinal Pigment Epithelium, but Not in the Presence of Triamcinolone Acetonide. Invest. Ophthalmol. Vis. Sci. 2008;49(13):486.
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Intravitreal anti-vascular endothelial growth factor (VEGF) treatment, such as with bevacizumab or ranibizumab, has been prevailed rapidly as a promising therapy for choroidal neovascularisation in age-related macular degeneration (AMD). However, there are only very limited data about their effect on normal eye tissue. For a good prognosis, not only the involution of choroidal neovasucularisaion but also the stability of the neighboring retinal pigment epithelium (RPE) is needed. We investigated the effect of bevacizumab and ranibizumab on the permeability of RPE in vitro.
RPE cells were isolated from enucleated porcine eyes. The second passage was cultured on 6-well membrane insert for about 4 weeks after confluence. Bevacizumab (0.0625mg/ml) or ranibizumab (0.05mg/ml) was added in the medium of the upper chamber, and 24 hours later the medium in both upper and lower chamber were replaced with fresh medium, containing fluoresceine isothiocyanate (FITC)-dextran in the upper medium. In some chambers, 10-5M of triamcinolone acetonide was added. After 5 hours, the medium from the lower chamber was collected and the fluorescence intensity was measured with a spectrofluorometer.
Bevacizumab and ranibizumab increased the permeability of the fluorescent label after 24 hours of stimulation. Even after completely removing these agents, the permeability increased significantly in avastin-treated cells up to the eighth day. On the other hand, lucentis-treated cells showed higher permeability only on the first day and, at the third day until eighth day, permeability was normal. Triamcinolone acetonide inhibited the permeability increase by these anti-VEGF agents significantly.
Bevacizumab and ranibizumab might cause the loss of junctional integrity of cultured RPE cells. Especially bevacizumab seems to cause the prolonged increase of permeability. Since triamcinolone significantly inhibited this effect, the combined therapy with Triamcinolone might be beneficial for the stability of RPE permeability after anti-VEGF treatment.
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