Navegando por Palavras-chave "neovascularização"

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    The effects of the subconjunctival injection of bevacizumab (Avastin®) on angiogenesis in the rat cornea
    (Academia Brasileira de Ciências, 2007-09-01) Barros, Luiz F.m.; Belfort, Rubens Junior [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    The purpose of this study was to evaluate the effects of the use of the subconjunctival injection of bevacizumab (Avastin®) on angiogenesis in the rat cornea. Corneas of 20 Wistar male rats were cauterized with silver nitrate crystal. Animals were divided in four groups: control group (GC) that received subconjunctivally 0.02 ml of 0.9% saline solution on the day of the lesion; group GO that received subconjunctivally 0.02 ml of bevacizumab just after the lesion; group G3 that received bevacizumab on day 3 and group G5 that received bevacizumab on day 5 after lesion. Animals were euthanized on day 7. The newly formed vessels were quantified after China Ink perfusion and photographs were obtained and analyzed in a computerized system (Image Pro-Plus®). In the control group, neovascularization covered 53.56% ± 15.11 (mean ± SD) of the corneal surface, compared with 35.57% ± 18.80 (mean ± SD) in the G0 group, 30.60%±11.82 (mean±SD) in the G3 and 35.86%±0.07 (mean±SD) in the G5. The results showed an inhibition of angiogenesis when the control group was compared with all treated groups. These results suggest that subconjunctival injection of bevacizumab is able to inhibit corneal angiogenesis independently of the day of treatment.
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    Fator de crescimento vascular endotelial na neovascularização corneana de camundongos
    (Universidade Federal de São Paulo (UNIFESP), 2014-09-30) Oliveira, Hailton Barreiros de [UNIFESP]; Siqueira, Wallace Chamon Alves de Siqueira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Angiogenesis is defined as the formation of new vessels from existing vessels. It is a complex multistep process that includes proliferative migration and differentiation of endothelial cells, degradation of extracelluar matrix, microtubule formation, and sprouting of new capillary branches. Angiogenic factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) have been used as angiogenic inducers. bFGF is the prototype member of 13 structurally related heparin-binding growth factors and it is known as a mitogen for several types of cells, including vascular endothelial cells and fibroblasts. Miquerol and collaborators have produced mice that express VEGF-LacZ. This was possible by inserting a gene identifier (reporter) 3i non-transcribed region of the endogenous VEGF gene. Thus, it was possible to produce VEGF mRNA containing the LacZ indentifier (reporter). The balance between angiogenic and antiangiogenic factors is responsible for the regulation of angiogenesis. Studies show the effects of a specific inhibitor of VEGF. VEGF TrapR1R2, which is a fusion protein of human Fc domain to the second domain and the third domain receptor R1 receptor R2 . This protein is able to sequester VEGF, antagonize and therefore prevent the formation of blood vessels. The objectives of this study are: demonstrate that mice cornea produces VEGF when stimulated by bFGF and to demonstrate that intraperitoneal administration of VEGF TrapR1R2 inhibits VEGF production and angiogenesis. Control pellets or pellets containing 80 ng bFGF were surgically implanted into wild-type C57BL/6 and VEGF-LacZ mouse corneas. The corneas were photographed, harvested, and the percentage of corneal NV was calculated. The corneas were evaluated for the expression of VEGF and neovascularization using Confocal Microscopy. VEGF-LacZ mice received tail vein injections of an endothelial-specific lectin after pellet implantation to determine the temporal and spatial relationship between VEGF expression and corneal NV using confocal microscopy. Western blot was used to analyze the presence of VEGF in corneas of mice that received wild implantation of pellets containing bFGF. Neovascularization was assessed on corneas that received the implant pellet containing bFGF after administration of intraperitoneal injections of VEGF TrapR1R2 or control IgG-Fc protein. NV of the corneal stroma began on day 4 and was sustained through day 21 following bFGF pellet implantation. Progression of vascular endothelial cells correlated with increased VEGF-LacZ expression. Western Blot analysis showed increased VEGF expression in the corneal NV zone. Following bFGF pellet implantation, the area of corneal NV in untreated controls was 1.05±0.12 mm² and 1.53±0.27 mm² at days 4 and 7, respectively. This was significantly greater than that of mice treated with VEGF TrapR1R2 (0.24±0.11 mm² and 0.35±0.16 mm² at days 4 and 7, respectively; p<0.05). The avascular cornea depends on a balance between various endogenous angiogenic factors (including VEGF , bFGF) and anti - angiogenic factors , when this balance is broken for some reason , corneal neovascularization occurs. This study suggests that the mice cornea produces VEGF when stimulated with bFGF. VEGF proteins are of great importance in corneal neovascularization, as function stimulating factors such as vascular endothelial cells. However, the specific mechanism of regulation of VEGF production by stimulation of bFGF has not yet been fully elucidated. It has been shown that injection of VEGF TrapR1R2 blocks the formation of blood vessels in the corneas of mice subjected to suturing. Using different technique to induce neovascularization, we demonstrate that VEGF TrapR1R2 blocks neovascularization in corneas that had implantation of sediments containing bFGF. More experiments are needed to dissect the role of bFGF in the production of VEGF and blocking using VEGF TrapR1R2. Probably, this mechanism contributes to the prevention of corneal neovascularization. The cornea of mice expressed VEGF after stimulation by bFGF. Systemic administration of VEGF TrapR1R2 blocks the vascularization of the mice cornea triggered by implanting pellets containing bFGF. Systemic administration of VEGF TrapR1R2 may have potential therapeutic applications in the management of corneal NV.