Retinopathies including age-related macular degeneration, diabetic retinopathy and retinopathy of pre-maturity are the leading causes of blindness and vision-related debilitation affecting millions world-wide and costing billions in Europe alone in health care expenses. These diseases can be viewed as vascular disorders as their progression is driven by deregulated growth of blood vessels (angiogenesis) and/or function (increased leakiness), properties intimately and causally linked to hypoxia in the retina. Understanding of how hypoxia-induced retinal angiogenesis operates in retinopathies is therefore of the outmost importance to understand these diseases as a whole and potentially find improved treatment options. We are attacking this very issue by using zebrafish - the only vertebrate model organism which withstand sufficiently low oxygen concentrations in the environment to allow for such studies.

We have found that hypoxia-induced retinal angiogenesis is a robust, concentration- and time-dependent process, and found that it follows a course closely associated with the clinical cause of angiogenesis in the eye of patients. This include waves of sprouting, vascular growth, anastomosis and maturation which move closer and closer to the center as hypoxia-exposure time increases thus engaging the more critical arterial portion of the vasculature to a higher and higher degree. I will in this talk present our most recent findings including some RNA-seq data indicating which molecules may be involved in this process, and invite the audience to a discussion on how best to model the process - which parameters are important and what further research is needed in order to produce strong mathematical models which could serve as a platform for discovering new important pathways and improving drug design and evaluation in the future.