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Peter Y Lwigale; Disruption of Cxcl12-Cxr4 chemokine signaling alters neurovascular patterning during ocular development. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4159.
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Ocular blood vessels and sensory nerves navigate through the periocular mesenchyme prior to the formation of a highly innervated and avascular cornea. The findings that the C-X-C motif chemokine ligand 12 (Cxcl12, also known as stromal cell-derived factor 1, Sdf-1) and its receptor Cxcr4 regulates the genesis and patterning of both neural and vascular networks in various tissues allow us to investigate their function during ocular development.
We analyzed the expression of Cxcl12 and Cxcr4 mRNA in the anterior eye during development. We utilized virus-mediated gene knockdown in avian together with cxcr4 knockout mice to examine what happens to ocular development in these mutants.
Our results show that Cxcl12 is expressed in the periocular mesenchyme surrounding the nascent ocular blood vessels, whereas the endothelial cells express Cxcr4. The expression patterns of both Cxcl12 and Cxcr4 are conserved in chick and mouse during ocular development. In addition, we show that Cxcl12 is also expressed by trigeminal neurons during gangliogenesis. We report that viral-mediated knockdown of Cxcl12 in tei1-H2B-YFP transgenic quail periocular mesenchyme causes severe vascular defects in the anterior eye. Similarly, knockdown of Cxcl12 in the trigeminal placode causes defects in gangliogenesis and diminished innervation of the cornea. Analysis of Cxcr4 mutants revealed defects in the periocular vasculature and decreased corneal innervation.
Combined, our results demonstrate that Cxcl12-Cxcr4 signaling plays a critical role in regulating the formation of both the vascular and sensory neural networks in the anterior eye during development.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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