The efficient treatment of many ocular diseases depends on the rapid diffusive distribution of solutes such as drugs or drug delivery vehicles through the vitreous humor. However, this multicomponent hydrogel possesses selective permeability properties, which allow for the diffusion of certain molecules and particles, whereas others are immobilized. In this study, we perform an interspecies comparison showing that the selective permeability properties of the vitreous are conserved across several mammalian species. We identify the polyanionic glycosaminoglycans hyaluronic acid and heparan sulfate as two key macromolecules that establish this selective permeability. We show that electrostatic interactions between the polyanionic macromolecules and diffusing solutes can be weakened by charge screening or enzymatic glycosaminoglycan digestion. Furthermore, molecule penetration into the vitreous is also charge-dependent and only efficient as long as the net charge of the molecule does not exceed a certain threshold.
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