You build me up, you break me down Molecular mechanisms of blood-retinal barrier development and disruption

Diabetes mellitus is a global epidemic, and it is predicted that the prevalence of diabetic patients increases from 382 million in 2013 to an estimated 592 million by 2035. Over one-third of diabetic persons has some form of diabetic retinopathy (DR), and approximately 5-10% develop vision-threatening complications such as proliferative DR and macular edema. Although disruption of the blood-retinal barrier (BRB) is an essential step in the development of retinal disease such as diabetic macular edema, its mechanisms are poorly understood. In this thesis, the formation of the BRB during early development at cellular and molecular levels is described, because understanding of physiological BRB formation may give us insights in the mechanisms of pathological BRB disruption. In addition, the role of plasmalemma vesicle-associated protein (PLVAP), a protein involved in retinal vascular leakage, is explored in BRB formation and disruption. Lastly, the contribution and possible mechanisms of inflammatory conditions in the development of diabetic macular edema and DR are critically evaluated.