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Purpose: To determine whether the co-injection of extracellular matrix degrading enzymes improves retinal transduction following intravitreal delivery of adeno-associated virus-2 (AAV2)., Methods: AAV2 containing cDNA encoding enhanced green fluorescent protein (GFP), under the control of a chicken β-actin promoter, was delivered by intravitreal injection to adult mice in conjunction with enzymes including collagenase, hyaluronan lyase, heparinase III, or chondroitin ABC lyase. Two weeks later, retinal flatmounts were examined for GFP expression using confocal microscopy., Results: Without the addition of enzymes, transduction was limited to occasional cells in the retinal ganglion cell layer. The addition of heparinase III or chondroitin ABC lyase greatly enhanced transduction of the retinal ganglion cell layer and increased the depth of transduction into the outer retina. Hyaluronan lyase had a limited effect and collagenase was ineffective. Electroretinograms survived with higher concentrations of heparinase III and chondroitin ABC lyase than were required for optimal retinal transduction., Conclusions: AAV2-mediated retinal transduction is improved by co-injection of heparinase III or chondroitin ABC lyase. Improved transduction efficiency may allow intravitreal injection to become the preferred route for delivering gene therapy to both the inner and outer retina., (© 2011 Molecular Vision)

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efficacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efficacy profile in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables., (Copyright © 2010 Elsevier Ltd. All rights reserved.)