The microvascular endothelial cells lining blood vessels in the brain/retina are held together by tight-junctions (TJ’s), a series of up to 30 interacting proteins that together form a tight seal limiting paracellular transport between adjacent cells. These TJ’s are a major constituent of the blood-brain and inner blood-retina barrier (BBB/iBRB) and have evolved for the specific purpose of protecting neural tissues from potentially damaging blood-borne agents such as viruses, bacteria and anaphylatoxins. One major component of the TJ, claudin-5, is highly enriched at the BBB/iBRB and has been shown to be an essential mediator of passive paracellular diffusion of molecules from the blood to the brain and vice-versa. Indeed, when first discovered, claudin-5 was termed “Transmembrane-protein-deleted-in-velo-cardio-facial-syndrome” (TMVCF), yet its role in the development of velo-cardio-facial syndrome (also known as 22q11DS) has never been explored. Recently, we have found an association with a genetic variant in the claudin-5 gene and the incidence of schizophrenia in a population of 22q11DS patients. We have also shown that this variant causes decreased claudin-5 protein expression compared to the normal gene. We hypothesise that claudin-5 levels in the brain microvasculature of 22q11DS patients could be a critical risk factor in pre-disposing an estimated 30% of patients who develop schizophrenia. In addition, claudin-5 levels play a critical role in co-ordinating brain and retinal microvascular development and given that up to 30% of 22q11DS patients develop retinal vein tortuosity, we wish to make a full assessment of retinal vascular patterning in patients in an attempt to reconcile any variations in claudin-5 levels to vascular phenotype. We wish to conduct a range of functional assays related to BBB/iBRB permeability and to correlate findings with clinical genotype and phenotype of 22q11DS patients. We hypothesise that the BBB/iBRB status of these patients could be a strong risk indicator for schizophrenia.