Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage.
OBJECTIVE
The Pathologische Anatomie Leiden-Endothelium (PAL-E) antigen is a marker for loss of the blood-brain barrier function in brain tumours. It is endothelium specific and is associated with the endothelial plasmalemmal vesicles (caveolae) involved in transcellular transport. To test whether blood-retinal barrier loss in diabetic retinopathy is associated with cellular changes in the endothelium, the expression of antigen PAL-E in relation to microvascular leakage in human diabetic retinopathy was investigated.


METHODS
Immunohistochemical staining of frozen tissue sections of postmortem eyes obtained from 30 persons without and 41 persons with diabetes mellitus was carried out with monoclonal antibodies against PAL-E and CD31 and with 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 eyes of diabetic patients and in 2 of the 30 normal control eyes. In the diabetic eyes, PAL-E staining co-localized with microvascular staining for endogenous fibrinogen, albumin and IgG. Strong staining for PAL-E was observed in sites without blood-tissue barriers, like the choroid.


CONCLUSIONS
In microvessels with an intact blood-retina barrier the endothelial antigen PAL-E is absent. Its expression is increased in 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 endothelium forms the cellular basis for microvascular leakage in diabetic retinopathy, rather than passive endothelial damage.
Schlingemann
R O
RO
Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, The Netherlands.
Hofman
P
P
Vrensen
G F
GF
Blaauwgeers
H G
HG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis*; D001813:Blood-Retinal Barrier; D003930:Diabetic Retinopathy / Q000276:immunology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000276:immunology*; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000032:analysis; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012171:Retinal Vessels / Q000276:immunology*
D000418:Albumins; D000954:Antigens, Surface; D007074:Immunoglobulin G; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005340:Fibrinogen