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Saptarshi Biswas, Julianne Chu, Galina Bachay, Dale D Hunter, William J Brunken; Laminin β2 and γ3 chains regulate microglial activation and the downstream effects of microglia on retinal vascular development. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3018.
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Microglia play important roles in vascular plexus formation both by mediating vascular anastomosis and secreting pro- or anti-angiogenic cytokines. Here, we investigated the role of laminin β2 and γ3 chains in recruiting retinal microglia to the developing vascular plexus, subsequent activation of microglia, and the effect of microglial activation states on retinal vascular development.
Global and activated microglia density in different regions of the retina, their association with vascular branch points, and mitotic and apoptotic endothelial cell quantification were analyzed using immunohistochemistry and 3D reconstruction.
Previously, we showed that there is an increase in the number of microglia associated with the vascular plexus in the laminin γ3-/- retina. Here, we show that the laminin γ3-/- retina has increased microglia density in the ganglion cell layer (GCL) both centrally and peripherally compared to wild type retina. Moreover, consistent with th in the laminin γ3-/- retina there is an increase in both the vascular branch points and microglia associated with them at the nascent plexus. In the laminin β2-/- retina, the normally orderly arrangement of microglia in the GCL is disrupted, and microglia aggregate around the persistent hyaloid vessels and malformed retinal vasculature. In the laminin γ3-/- retina, more activated microglia are present around the vascular plexus than in the wild type. The increased number of vascular branch points associated microglia in the laminin γ3-/- retina suggests more anastomotic events, leading to a denser plexus. In contrast, in the laminin β2-/- retina, the number of activated microglia remains the same. The developing vascular plexus of the laminin γ3-/- retina also has increased endothelial cell proliferation compared to the wild type, whereas the number of apoptotic endothelial cells remains unchanged in the laminin γ3-/- retina compared to the wild type.
Our results suggest that laminins containing the β2 and γ3 chains differentially regulate distribution of microglia in the retina as well as the recruitment of microglia to the developing vascular plexus with β2 laminins having pro-angiogenic effects and γ3 laminins having anti-angiogenic effects.
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