Project: C05

Galectins in the pathogenesis of retinal neovascular and inflammatory diseases

Dysfunctional humoral and cellular innate immunity are key components in the development and progression of age-related macular degeneration (AMD). Retinal microglia, the tissue resident immune cells, play pivotal roles in innate immune responses and regulation of tissue integrity. While a short period of microglia activation supports homeostasis, chronic microglia reactivity represents a driving force for retinal cell death and disease. We have previously shown that polysialic acids form a protective layer on retinal cells and that their binding to microglial receptors is strongly anti-inflammatory, indicating a crucial role for glycoproteins in retinal immunity. In very recent experiments, we demonstrated that galectin-3, a member of the β-galactoside-binding lectin family is strongly upregulated in reactive microglia in retinas of dry AMD patients and in two different corresponding mouse models. In this project, the student will identify the role of dysregulated galectins in AMD with a focus on microglia reactivity, neurodegeneration and neovascularization in the retina. The techniques that will be used to carry out the project will include in vitro and animal models, immunohistochemistry, FISH, ELISAs, RNA analysis, pathway and cell signaling analysis, cell transcriptomics.