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J. Singh, T. L. Jackson, O. A. Anderson, A. A. Hussain, J. Marshall; Effect of Pathlength on Trans-Scleral Macromolecular Diffusion. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5826.
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To quantify the effect of pathlength (scleral thickness) on trans-scleral albumin diffusion.
Anterior superotemporal scleral specimens were obtained from 12 donor eyes. Sclera was dissected to obtain inner sclera, outer sclera, and full-thickness sclera for each eye. Scleral specimens were mounted in a modified Ussing chamber with fluorescein isothiocyanate labelled, 66kDa, bovine albumin in the hemichamber facing the internal scleral surface. The rate of trans-scleral diffusion was determined over 24 hours, at 25°C, with a spectrophotometer. Scleral thickness was measured using gluteraldehyde fixed sections and a sliding graticule, taking the mean of 15 randomly selected sections for each specimen.
Mean scleral thickness (+/-1SD) was 547+/-167, 629+/-145, and 761+/-183 microns for inner, outer, and full-thickness sclera respectively. Trans-scleral diffusion was 15.7+/-5.3, 15.7+/-10.7, and 9.9+/-3.5 x10-3 picomoles/mm2/hr respectively. There was no significant difference in permeability comparing inner and outer sclera. There was an inverse linear relationship between pathlength and the rate of diffusion (p 0.008).
Quantifying the transscleral diffusion of a 66 kDa protein and its relationship to scleral thickness may guide novel strategies of drug delivery. In particular, these data suggest that reduced scleral thickness should improve the trans-scleral delivery of high molecular weight agents.
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