Altered expression of retinal occludin and glial fibrillary acidic proteinin experimental diabetes

PURPOSE. TO investigate how diabetes alters vascular endothelial cell tight junction protein and glial cell morphology at the blood-retinal barrier (B RB). METHODS. The distribution of the glial marker, glial fibrillary acidic prot ein (GFAP), and the endothelial cell tight junction protein occludin were e xplored by immunofluorescence histochemistry in flatmounted retinas of stre ptozotocin (STZ)-diabetic and age-matched control rats, and in BB/Wor diabe tes-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 an d increased GFAP immunoreactivity in small groups of Muller cells. After 4 months of STZ-induced diabetes, all Muller cells had intense GFAP immunorea ctivity, whereas there was virtually none in the astrocytes. BB/Wor diabeti c rats had similar changes in GFAP immunoreactivity. Occludin immunoreactiv ity 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 post capillary venules. Diabetes reduced occludin immunoreactivity in the capill aries 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 th e STZ-diabetic rats. CONCLUSIONS. Diabetes alters GFAP expression in retinal glial cells, accomp anied by reduction and redistribution of occludin in endothelial cells. The se changes are consistent with the concept that altered glial-endothelial c ell interactions at the BRB contribute to diabetic retinopathy.