Project: A04

Metabolic control of corneal hem- and (lymph)angiogenesis

Pathological corneal hem- and lymphangiogenesis is an important component of various blinding corneal diseases and represents an important target in therapeutic interventions. Accumulating recent evidence indicate that endothelial cell (EC) metabolism is intimately linked to EC function and centrally controls vascular growth. We and others could recently show that neoangiogenesis requires a dynamic and timely mitochondrial metabolic switch to guarantee cellular growth under energetically demanding angiogenic processes. The profound metabolic plasticity of ECs does not only safeguard vascular growth under challenging nutrient conditions but also decisively control different cellular components of tissues, in particular, immune cells such as macrophages by releasing distinct metabolites. Our recent data providesed genetic evidence for the involvement of mitochondria in neovascularization (under disease and regenerative conditions) by coordinating the tissue metabolic and inflammatory crosstalk. Here we aim to explore the mitochondrial control of pathological angiogenesis in corneal neovascular diseases.

Key methods: transgenic mouse models, in vivo mouse models, metabolomics, cytokine bead arrays, q-RTPCR, flow cytometry, cell culture assays, ex vivo assays