Proposed mechanism by which Jam-A regulates corneal inflammation, neovascularization, and scarring.

<p>Jam-A negatively governs VEGF-A expression thereby regulating VEGFR-2 signaling pathway. The VEGF-A/VEGFR-2 pathway leads to angiogenesis as well as recruits inflammatory cells. The VEGF-A/VEGFR-2 pathway also has a positive feed back loop with TGFβ pathway that along with ECM remodeling leads to scarring. Introduction of silk suture results in inflammation leading to neovascularization and no scarring due to the presence of an intact Descemet's membrane. Full thickness wounds that cause a break in the Descemet's membrane lead to ECM remodeling and TGFβ pathway activation that together can lead to scarring. Jam-A deficient mice exhibit increased VEGF-A/VEGFR-2 signaling and demonstrate increased inflammation, angiogenesis as well as scarring compared to WT mice.