Invited Speaker: Facilitated Drug Delivery to the Retina by Controlled Modulation of Permeability at the Inner Blood-retina Barrier

The inner retina is suffused with a network of fine capillaries, rendering, in principle, the concept of systemic ocular drug delivery highly attractive. However, as with the vasculature of the brain, endothelial cells lining the inner retinal vessels are sealed by ‘tight-junctions’ comprising over 30 proteins, these representing the inner blood-retina barrier (iBRB). While barrier integrity is of obvious and critical importance, the iBRB nevertheless prevents an estimated 98% of systemically deliverable low molecular weight potentially therapeutic drugs from gaining access to retinal tissues and, where the iBRB remains intact in the presence of edema, it prevents fluid from getting out. In fact, permeability at the iBRB can be controlled with precision, quite simply, by down-regulating selected tight junction transcripts in such a manner that low molecular weight compounds can now move from the peripheral circulation into the retina, but larger (>1,000 Dalton), potentially neurotoxic compounds such as anaphylatoxins, antibodies, viruses etc., are prevented from doing so. Here, we provide a description of the fundamental experimental technology, together with examples of how it can be used in protecting the retina in chronic and acute disease states.