Chapter 5. Evaluating vascular leak in vivo

Vascular permeability during normal physiology is necessary, reversible, and highly regulated. At the site of an injury, hyperpermeable blood vessels allow deposition of fibrin which can form a barrier to contain the wound and prevent infection. Likewise, ongoing extravasation or transendothelial migration of immune cells is necessary for surveillance of tissues. In contrast, uncontrolled vascular leak occurs as a side effect in a number of pathologies including age-related macular degeneration, ischemic disease, cancer, and lung injuries. During the progression of disease, permeability is often dysregulated and results in ongoing accumulation of edema, which exacerbates disease and prevents recovery. An expanding number of mouse models to assess permeability in vivo have led to the design of new therapies and approaches to limit pathological hyperpermeability. This chapter will describe several mouse models which can be used to directly test the pro- or anti-permeability properties of novel compounds, as well as mouse models of ischemic disease in which hyperpermeability plays a key role. These methods can be used to evaluate the efficacy of potential new antileak therapies and to dissect the molecular mechanisms regulating permeability in vivo.