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In vitro transcorneal and transscleral diffusion of radiolabeled compounds in human and rabbit cornea and in human, monkey, dog, and rabbit sclera
Author(s) -
STRUBLE CB,
EDELHAUSER HF,
HOLLEY GP,
GROSSNIKLAUS HE
Publication year - 2009
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2009.2426.x
Subject(s) - sclera , cornea , dexamethasone , rabbit (cipher) , lagomorpha , ophthalmology , chemistry , dextran , histology , anatomy , medicine , pathology , endocrinology , chromatography , statistics , mathematics
Purpose To determine the in vitro diffusion of selected compounds across the cornea or sclera of humans, monkeys, dogs, and rabbits. Methods Human and NZW rabbit corneas were obtained and the epithelium was removed from one cornea of each pair. Corneas were mounted in chambers with 3H‐water or 3H‐dexamethasone on the epithelial side and BSS solution on the endothelial side. Serial aliquots were taken from each chamber and assayed by LSC. Scleral sections from human, NZW rabbit, dog, or monkey eyes were mounted in perfusion chambers. Adjacent sclera was used for H&E histology. 3H‐water, 3H‐dexamethasone, or 70kD‐14C‐dextran were added to the episcleral surface while perfusing BSS across the choroidal side. Serial aliquots were collected up to 5 hrs and assayed by LSC. Scleral permeability (ktrans) was calculated. H&E slides were used to determine scleral thickness. Results 3H‐water diffused through cornea faster than 3H‐dexamethasone, especially with denuded epithelium. Scleral thickness and molecular weight were determinant of diffusion in sclera. Monkey sclera was thinnest, followed by dog, rabbit, and human. ktrans for 70kD‐14C‐Dextran and 3H‐dexamethasone were greatest in monkey, followed by dog, rabbit, and human. ktrans values for 3H‐water were similar in all species, and greater than values for 14C‐dextran and 3H‐dexamethasone. Conclusion These studies demonstrate permeability of cornea and sclera in human and animal models with compounds of varied molecular weights representative of drugs being developed for treatment of ocular diseases. The results of this study indicate that these techniques are valuable as screening tools in the development of ocular drugs.