29: Impact of HSV-1 induced VEGF-A on corneal lymphangiogenesis during the development of herpetic stromal keratitis

Much of the research regarding lymphangiogenesis and disease has focused on lymphedema and cancer biology. There is still much to be elucidated regarding the impact of lymphatic vessel development during microbial pathogenesis. One function of lymphatic vessels is to drain soluble antigen and antigen-presenting cells from the periphery to the draining lymph nodes, facilitating the mobilization of an adaptive immune response. However, the resulting immune response can lead to detrimental tissue pathology. This is extremely important during ocular disease, wherein transparency of the tissues anterior to the retina is required for normal vision. Herpes simplex virus type-1 (HSV-1) infection of the cornea can result in herpetic stromal keratitis (HSK), an immunopathologic condition characterized by opacity, edema, and neovascularization of the cornea. The impact of hemangiogenesis during an HSV-1 ocular infection has been well studied; however, the impact of lymphangiogenesis in the cornea has only recently been investigated. Previous studies indicate HSV-1 induces lymphangiogenesis via the expression of VEGF-A by infected cornea epithelial cells during acute infection. Furthermore, blood and lymphatic vessels were found throughout the corneas of latently infected animals (day 30 post-infection (pi)). The goal of the current study is to identify the growth factors and cells that contribute to the maintenance and further development of lymphatic vessels in the cornea following the resolution of infection. Results indicate there is a substantial increase in LYVE-1-postive lymphatic vessels by day 14 pi, when HSK develops. Preliminary analysis of 20 growth factors and cytokines revealed robust expression of IL-6, IL-1β, HGF, MMP9, and VEGF-A preceding day 14 pi. It is anticipated that results from this study may lead to new treatment strategies to attenuate the development of HSK.