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发布于:2019-5-16 23:27:17  访问:79 次 回复:0 篇
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Low cytometry plots of granulocytes within the posterior segment in the
In sharp contrast to the larger proportion of inflammatory cells in the peripheral blood of C3-/- mice, immune cell infiltration of the eyes was Kinase inhibitor-1price markedly suppressed by C3 deficiency. RPE cells also contribute to the VEGF-VEGFR1 axis. It is likely that macrophage/monocyte recruitment into the eye and the upregulation of VEGF expression are suppressed in C3-/- mice because of the absence of C3a and C5a. Moreover, the inhibition of laser-induced CNV in C3-/- mice is likely to be due to the reduction of VEGF expression in the eye. However, further studies are still required to identify the role of C3 in the production of VEGF by RPE cells and to clarify whether locally or systematically produced C3 plays a pivotal role. Blockade of the complement pathway is a new strategy for the treatment of AMD. Many new drugs are currently being studied in clinical trials. POT-4 (Potentia Pharmaceuticals, Louisville, KY) is a peptide capable of binding to human complement factor C3 and preventing its activation, and a phase I clinical trial of POT-4 for exudative AMD has been completed40. Our findings provide additional evidence that an ocular C3-targeting agent is likely to be effective in the treatment of exudative AMD.Scientific RepoRts | 5:15702 | DOi: 10.1038/srepwww.nature.com/scientificreports/Figure 3. Lack of C3 affected the recruitment of macrophage/monocyte subsets to the posterior segment of the eye. (A) Representative flow cytometry plots of macrophages/monocytes in the posterior segment of the eye from WT and C3-/- mice without laser treatment and at 1, 3, and 7 days PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21231855 just after injury.Low cytometry plots of granulocytes within the posterior segment of your eye from WT PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24756377 and C3-/- mice devoid of laser remedy and at 1, three, and 7 days just after injury. The regions surrounded by ovals include CD11b+Ly6G+ cells. (B) Ratios of CD11b+Ly6G+ cells (oval region within a) to total number of live cells. *P < 0.05 compared with WT mice. Six mice were used to give a single value; n = 3 in each experiment.occurs 1 day after laser injury9,36. However, others have reported that neutrophil infiltration is maximal at 3 days after laser injury in wild-type mice13. All studies concur that macrophage infiltration peaks on day 3 after laser injury9,36,37. In our study, granulocytes and all three macrophage subsets showed maximal infiltration into the posterior segment of the eyes of wild-type mice 3 days after laser treatment. However, in C3-/- mice, the proportions of intraocular granulocytes and Ly6Chi macrophages were maximal at 1 day after laser injury, whereas Ly6Cint macrophages were maximal at 3 days and the proportion of Ly6Clo macrophages increased until at least 7 days. In sharp contrast to the larger proportion of inflammatory cells in the peripheral blood of C3-/- mice, immune cell infiltration of the eyes was markedly suppressed by C3 deficiency. It is likely that tissue migration and the recruitment of immune cells were inhibited because of the lack of C3a and C5a anaphylatoxins. It is also plausible that when the number of inflammatory cells infiltrating the eyes is increased, a feedback loop may occur and reduce the number of inflammatory cells in the peripheral blood38.
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