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Anthony Mukwaya, Beatrice Bourghardt Peebo, Maria Xeroudaki, Zaheer Ali, Lasse Jensen, Neil S Lagali; Induced capillary remodelling in inflammatory ocular angiogenesis model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3523. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Mechanisms for microvascular remodelling and capillary maturation are not fully understood. Here, we hypothesise that in pathology, signalling pathways that lead to rapid microvascular remodelling are independent of the VEGF-A axis.
The suture-induced corneal neovascularisation model in rats was used, involving male Wistar rats sutured temporally in the cornea with two nylon sutures at 1.5mm from the limbus. When the new capillary sprouts had invaded the cornea to 50% of the distance to the suture, (time point 0h), rats were divided into a suture IN group, where sutures were maintained and corneas sampled at 24, 72 and 120h (4 cornea/time point), and a suture OUT group, in which sutures were removed at 0h to induce remodelling, and then sampled at the same time points as described above. 4 non-sutured cornea served as controls. A slit lamp camera was used to track vascular density dynamics and in vivo confocal microscopy to monitor inflammatory cell infiltration and changes in morphology of single capillaries. Microarrays were used to monitor whole transcriptome changes at 24 h time point. Analysis of variance (ANOVA) was used for group comparisons, P value < 0.05= significant.
Removal of the angiogenic stimulus effected a granulocyte-to-macrophage transition (P = 0.01-to-P = 0.004), and vascular density decreased starting at 72h relative to suture IN (P = 0.04). VEGF-A expression reduced with suture removal (P<0.001). Also many other proinflammatory, proangiogenic, and promaturation genes were deferentially regulated between suture IN and suture OUT at 24h time point.
Early microvascular maturation in our model is not exclusively dependent upon VEGF-A, but also involves other signalling pathways of potential therapeutic interest.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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