The Influence of Intraocular Pressure on the Transscleral Diffusion of High Molecular Weight Compounds

Abstract

Abstract: : Purpose. To evaluate the effects of intraocular pressure on the permeability of human sclera to high molecular weight compounds. Methods. The scleral permeability to FITC-Albumin (70 kD) and FITC-Dextran (70 kD) was determined at transscleral pressures from 0 to 60 mm Hg. For each compound at each pressure 6-8 experiments were performed. Scleral sections excised from moist-chamber stored human globes were mounted in a two-compartment perfusion chamber. A small depot of drug (500 µl of 10^-4 M in BSS) was added to the episcleral surface. BSS was perfused to the choroidal side for up to 24 hours. For each compound experiments were performed at transscleral pressures of 0, 15, 30, 60 mm Hg. Temperature was maintained at 37°C. Fractions of choroidal perfusate were collected and fluorescence was measured with a spectrofluorometer. From this data, scleral permeability K_trans (cm/sec) was calculated. Results. Human scleral permeability to FITC-Albumin was significantly lower at 15 mm Hg compared to 0 mm Hg (P<0.05). No significant differences were observed between 15 and 60 mm Hg (P>0.05). Transscleral pressures between 0 and 60 mm Hg did not significantly alter the scleral permeability to FITC-Dextran (P>0.05). Conclusions. Human sclera was more permeable to the globular shaped FITC-Albumin than to the linear FITC-Dextran molecule of the same molecular weight. Permeability to FITC-Albumin was significantly decreased elevating pressure from 0 to 15 mm Hg, while no additional decrease was observed raising pressure from 15 to 60 mm Hg. No significant differences in permeability to FITC-Dextran were observed at pressures from 0-60 mm Hg. These experiments suggest that high molecular weight compounds (e.g. immunoglobulins, oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.

Keywords: sclera • intraocular pressure • retina