Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group.
OBJECTIVE
To investigate how diabetes alters vascular endothelial cell tight junction protein and glial cell morphology at the blood-retinal barrier (BRB).


METHODS
The distribution of the glial marker, glial fibrillary acidic protein (GFAP), and the endothelial cell tight junction protein occludin were explored by immunofluorescence histochemistry in flatmounted retinas of streptozotocin (STZ)-diabetic and age-matched control rats, and in BB/Wor diabetes-prone and age-matched diabetes-resistant rats.


RESULTS
GFAP immunoreactivity was limited to astrocytes in control retinas. Two months of STZ-diabetes reduced GFAP immunoreactivity in astrocytes and increased GFAP immunoreactivity in small groups of Müller cells. After 4 months of STZ-induced diabetes, all Müller cells had intense GFAP immunoreactivity, whereas there was virtually none in the astrocytes. BB/Wor diabetic rats had similar changes in GFAP immunoreactivity. Occludin immunoreactivity in normal rats was greatest in the capillary bed of the outer plexiform layer and arterioles of the inner retina but much less intense in the postcapillary venules. Diabetes reduced occludin immunoreactivity in the capillaries and induced redistribution from continuous cell border to interrupted, punctate immunoreactivity in the arterioles. Forty-eight hours of insulin treatment reversed the pattern of GFAP and occludin immunoreactivity in the STZ-diabetic rats.


CONCLUSIONS
Diabetes alters GFAP expression in retinal glial cells, accompanied by reduction and redistribution of occludin in endothelial cells. These changes are consistent with the concept that altered glial-endothelial cell interactions at the BRB contribute to diabetic retinopathy.
Barber
A J
AJ
The Ulerich Ophthalmology Research Laboratory. Departments of Ophthalmology and. Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania.
Antonetti
D A
DA
Gardner
T W
TW
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001813:Blood-Retinal Barrier; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D062793:Occludin; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology
D005136:Eye Proteins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat