Urethane-induced rat retinopathy. Plasticity of the blood-retinal barrier in disease

Sodium fluorescein and fluoresceinated dextrans penetrate the blood-retinal barrier (BRB) of rats with urethane-induced retinopathy. We have extended these observations, using horseradish peroxidase (HRP) as an ultrastructural probe of the BRB. Intravenous HRP penetrated the BRB 7 weeks after urethane treatment began. This occurred where retinal capillaries invaded the retinal pigment epithelium (RPE) after photoreceptor degeneration. The penetration intensified with duration of the retinopathy, but remained localized near intraepithelial capillaries. The mechanisms by which HRP penetrated the BRB changed as the retinopathy progressed. In the earliest stages (7-10 weeks of age) vesicular transport across endothelia and/or leakage from the choriocapillaris into the pericapillary space of intraepithelial capillaries and then along this space into the retina. At later stages, two more mechanisms were at work: (1) fenestrae developed in the intraepithelial capillaries, and (2) the RPE attenuated, losing its barrier function. Except where this occurred, intercellular RPE junctional complexes remained intact and retarded HRP. We suggest that the rat urethane retinopathy models the plasticity of BRB components--RPE and endothelia--over the course of retinal disease.