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Deniz Hos, Konrad Koch, Felix Bock, Claus Cursiefen, Ludwig Heindl; Serum eye drops promote vascular endothelial cell proliferation in vitro and antagonize (antiangiogenic) VEGF blockade in vivo. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2086.
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Autologous serum eye drops lead to faster wound closures and help treating non-healing and relapsing corneal ulcerations. Although having a well defined wound-healing profile, the influence of serum eye drops on corneal neovascularization is so far unclear. We therefore analyzed the corneal vascular effects of serum eye drops in comparison as well as in combination with topical VEGF blockade.
For in vitro studies, human blood or lymphatic endothelial cells (BEC or LEC, respectively) were treated with 10% fresh serum, 50 ng/ml Bevacizumab or a combination of both. Endothelial cell proliferation was assessed after 48 hours using a BrdU-based ELISA. For in vivo studies, inflammatory corneal neovascularization was induced by suture placement in BALB/c mice (n=8 per group). Mice then received serum or Bevacizumab eye drops (3x daily, respectively) or a combination of both (3x daily for each treatment). After one week, corneal wholemounts were stained for blood (CD31) and lymphatic (LYVE-1) vessels.
In vitro, serum addition significantly increased whereas Bevacizumab significantly reduced endothelial cell proliferation (BEC: serum mean m= +55.3%, p<0.01; Bevacizumab m= -13.6%, p<0.05; LEC: serum m= +9.5%, p<0.01; Bevacizumab m= -33.0%, p<0.01). The combined treatment with serum and Bevacizumab led to cell proliferation levels that presented between the monotreated groups (BEC: m= +42.2%, p<0.05; LEC: m= -5.9%, p>0.05). In vivo, inflammatory corneal hem- and lymphangiogenesis was not influenced by treatment with serum eye drops, whereas treatment with Bevacizumab significantly reduced blood and lymphatic vessel growth (hemangiogenesis: serum m= +9.5%, p>0.05; Bevacizumab m= -19.8%, p<0.05; lymphangiogenesis: serum m= -7.8%, p>0.05; Bevacizumab m= -33.3%, p<0.05). The combination of serum and Bevacizumab eye drops attenuated the anti(lymph)angiogenic effect of Bevacizumab (hemangiogenesis: m= -8.4%, p>0.05; lymphangiogenesis: m= -15.2%, p>0.05).
Although promoting blood and lymphatic endothelial cell proliferation in vitro, serum eye drops show no significant impact on inflammatory corneal hem- and lymphangiogenesis in vivo. Interestingly, serum eye drops seem to antagonize the anti(lymph)angiogenic effect of topical VEGF blockade.
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