Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage

Aims/hypothesis. The Pathologische Anatomie Leiden-Endothelium (PAL-E) anti gen is a marker for loss of the blood-brain barrier function in brain tumou rs. It is endothelium specific and is associated with the endothelial plasm alemmal vesicles (caveolae) involved in transcellular transport. To test wh ether blood-retinal barrier loss in diabetic retinopathy is associated with cellular changes in the endothelium, the expression of antigen PAL-E in re lation to microvascular leakage in human diabetic retinopathy was investiga ted. Methods. Immunohistochemical staining of frozen tissue sections of postmort em eyes obtained from 30 persons without and 41 persons with diabetes melli tus was carried out with monoclonal antibodies against PAL-E and CD31 and w ith antibodies against endogenous fibrinogen, albumin and IgG as indicators of vascular leakage. Results. Patchy or uniform microvascular PAL-E staining was observed in the retina of 17 of the 41 eves of diabetic patients and in 2 of the 30 normal control eves. In the diabetic eyes, PAL-E staining co-localized with micro vascular staining for endogenous fibrinogen, albumin and IgG. Strong staini ng for PAL-E was observed in sites without blood-tissue barriers, like the choroid. Conclusions/interpretation. In microvessels with an intact blood-retina bar rier the endothelial antigen PAL-E is absent. Its expression is increased i n retinal vessels of patients with diabetic retinopathy and correlates with microvascular leakage of plasma proteins. This phenotypic shift involving an antigen associated with caveolae suggests that dysfunction of the endoth elium forms the cellular basis for microvascular leakage in diabetic retino pathy, rather than passive endothelial damage.