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Sarah A. Molokhia, Kongnara Papangkorn, Donald Mix, Charlotte Butler, Kavita Gupta, Prasoona Karra, John W. Higuchi, Balbir Brar, S Kevin Li, William I. Higuchi; Importance of the Conjunctiva in Transscleral Iontophoresis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3249.
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The objective was to examine the importance of conjunctiva as a potential barrier in transscleral iontophoresis. The approach was to study the in vitro transport of a low and a high molecular weight compound across the conjunctiva and sclera composite membrane and across the sclera alone under constant current iontophoresis.
Passive and anodal transport studies in vitro were performed using a side-by-side diffusion cell with excised ocular tissues from New Zealand White rabbits. Each compartment of the diffusion cell had a 2-ml volume and an effective diffusional area of 0.2 cm2. The conjunctiva + sclera composite membrane or the sclera alone was sandwiched between the two half-cells with the choroid side facing the receiver chamber. Silver foil and AgCl were used as the conductive elements in anodal iontophoresis. 14C-mannitol and FITC-dextran 70 KDa were the permeants of interest and assayed by liquid scintillation counting and UV spectrophotometry, respectively.
The passive permeability values for both 14C-mannitol and dextran 70KDa across sclera alone were found to be 2 to 3 times greater than with the conjunctiva + sclera composite. During anodal iontophoresis, the 14C-mannitol permeability values for sclera alone and for conjunctiva + sclera were similar, while with dextran 70KDa, the permeability value for sclera alone was around 2 times greater than that of conjunctiva + sclera. This suggests that the conjunctiva under anodal iontophoresis presents itself as a potential barrier for the transport of dextran 70KDa (large molecule) but not for 14C-mannitol (small molecule).
The results demonstrate the possible importance of conjunctiva as a barrier during anodal iontophoresis of macromolecules (e.g., anti-VEGF drug molecules that are 50 KDa or larger) and suggests considering the use of the conjunctiva + sclera composite membrane in in vitro experiments aimed as predicting transscleral iontophoresis in vivo.
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