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

From the Department of Ophthalmology, Emory University, Atlanta, Georgia; and the Department of Ophthalmology, University Hospital of Maastricht, The Netherlands.

PURPOSE. To evaluate the effects of intraocular pressure on the permeability of the human sclera to high-molecular-weight compounds.

METHODS. Human transscleral permeability to FITC-albumin (70 kDa) and 70-kDa and 150-kDa FITC-dextran was determined at transscleral pressures from 0 to 60 mm Hg. For each compound at each pressure, six to eight experiments were performed. Scleral sections were mounted in a two-compartment perfusion chamber. Temperature was maintained at 37°C. Fractions of choroidal perfusate were collected, and fluorescence was measured with a spectrofluorometer. From these data, scleral permeability K_trans (in centimeters per second) was calculated.

RESULTS. Permeability to FITC-albumin was decreased by approximately one half when pressure was elevated from 0 to 30 mm Hg (P < 0.05). No significant differences in permeability to 70-kDa FITC-dextran were observed at pressures from 0 to 60 mm Hg. Permeability to 150-kDa FITC-dextran decreased by a little more than one half when transscleral pressure was raised from 0 to 15 mm Hg and was approximately 10 times lower at 60 mm Hg than at 0 mm Hg (P < 0.01).

CONCLUSIONS. Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mm Hg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mm Hg a 10-fold decrease was observed compared with that at 0 mm Hg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.

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