RETINAL VASCULAR ENDOTHELIAL-CELL ENDOCYTOSIS INCREASES IN EARLY DIABETES

BACKGROUND: Several physiological studies in recent years have convinc ingly demonstrated increased clearance of intravascular protein tracer s by several different tissues, including the retina, during early dia betes and galactosemia in the rat. This change has been described as a consequence of increased permeation, although vascular leakage has no t been demonstrated, and the fate of such tracers remains unelucidated . EXPERIMENTAL DESIGN: A pilot study in this laboratory showed no evid ence of vascular leakage but suggested increased endocytosis of horser adish peroxidase (HRP) by retinal vascular endothelial cells (RVECs) i n early diabetes. We therefore quantified RVEC endocytosis in normal, streptozotocin (STZ)-treated nondiabetic and STZ-diabetic rats using t he design-based stereology method of ''vertical sections.'' A duration of diabetes (6 weeks) was chosen to approximate the time period in wh ich other workers have demonstrated increased protein permeation of th e retina. RESULTS: After a 20-minute exposure to the tracer, HRP react ion product was observed in small vesicular and tubular endosomes and larger multivesicular bodies of the RVECs. Stereological analysis reve aled a 6.5 fold increase in the volume of HRP-containing organelles in the RVECs of diabetic rats compared with STZ-treated nondiabetics or normal controls. None of the animals in this study showed HRP reaction product outside the retinal vascular endothelium. CONCLUSIONS: A high ly significant increase in RVEC endocytosis occurs in early diabetes. Increased RVEC endocytosis may contribute to the observed clearance of intravascular protein tracers by the retina during early diabetes.