Barrier modulation in drug delivery to the retina

The inner blood-retina barrier (iBRB) is essential in restricting the movement of systemic components such as enzymes, anaphylatoxins, or pathogens that could otherwise enter the neural retina and cause extensive damage. The barrier has evolved to confer protection to the delicate microenvironment of the retina, and the tight junctions located between adjacent microvascular endothelial cells can restrict the passage of up to 98% of clinically validated low-molecular-weight therapeutics which could hold significant promise for a range of degenerative retinal conditions. Here, we describe a method for the selective RNAi-mediated targeting of one component of the tight junction, claudin-5. We outline the generation of a doxycycline inducible adeno-associated viral vector for the localized, inducible, and size-selective modulation of the iBRB and describe how this vector can be used in ophthalmology research.