Blood-aqueous barrier can be circumvented by lowering intraocular pressure

Rhesus monkeys were injected intravenously with hypertonic urea (9 ml/kg body weight of 30% urea in 10% invert sugar) and the intraocular pressure was measured with an applamatic tonometer. When this pressure reached its minimum (20% of the normal value) horseradish peroxidase (molecular weight 40,000; radius of an equivalent hydrodynamic sphere about 2.5 nm; 0.5 g/kg body weight), was injected intravenously. Twenty minutes following peroxidase administration, either aqueous humor was sampled from the anterior chamber for biochemical determination of peroxidase activity, or one eyeball was enucleated and processed for light and electron microscopic localization of the enzymatic tracer. This experiment showed that: (1) therapeutic doses of hypertonic urea do not cause a breakdown of either the blood-retina or the blood-aqueous barriers; (2) as intraocular pressure decreases, peroxidase-containing blood flows back from the episcleral veins into the Schlemm canal; (3) macromolecules up to the dimensions of horseradish peroxidase leak through the intercellular clefts of the endothelium of the Schlemm canal, permeate the juxtacanalicular connective tissue and trabecular meshwork, and finally enter the anterior chamber. Thus, blood-borne substances can circumvent the blood-aqueous barrier when intraocular pressure is decreased, and administration of a hypertonic agent may represent a simple pharmacological device to cause penetration into the ocular chambers by drugs that are normally excluded from the interior of the eye.