PATHOLOGICAL UP-REGULATION OF INNER BLOOD-RETINAL BARRIER GLUT1 GLUCOSE-TRANSPORTER EXPRESSION IN DIABETES-MELLITUS

The pathological changes in the retinal microvasculature characteristi c of diabetic retinopathy (DR) are the result of chronic exposure to e levated blood glucose. Since glucose entry into the microvascular endo thelial cells comprising the inner blood-retinal barrier (BRB) is medi ated by the GLUT1 glucose transporter, changes in GLUT1 expression on the inner BRB in long-standing diabetes mellitus may have a direct imp act on the subsequent development of retinopathic changes. In the pres ent study, quantitative immunogold electron microscopy for GLUT1 was e mployed on ultrathin cross-sections of postmortem retina specimens fro m 3 individuals with long-standing diabetes and minimal or no clinical retinopathy and from 2 non-diabetic individuals without ocular disord ers. In the non-diabetic retinal capillaries, GLUT1 immunogold was dis tributed asymmetrically between the lumenal and ablumenal membranes wi th a lumenal-to-ablumenal ratio of 1 to 1.7. In the diabetic microvess els, a bimodal distribution pattern of GLUT1 immunoreactivity was obse rved. In 17 of 40 of the diabetic microvessels examined, the density a nd distribution of GLUT1 was no different from that of the non-diabeti c vessels; however, in a subpopulation of the diabetic microvessels (2 3 of 40), a dramatic increase in GLUT1 immunoreactivity on the lumenal and albumenal membrane and in the cytoplasm was noted. On the lumenal membrane, the increased expression of immunoreactive GLUT1 was more t han 18 times that of the non-diabetic microvessels. These findings dem onstrate that localized upregulation of GLUT1 expression at the inner BRB occurs in long-standing diabetes mellitus with minimal or no clini cal retinopathy and suggest that this upregulation may serve to amplif y the deleterious effects of chronic hyperglycemia on the retinal micr ovasculature.