Aldose reductase and pericyte-endothelial cell contacts in retina and optic nerve

Normally, direct contacts between pericytes and endothelial cells occur frequently in both retinal and optic nerve capillaries. The contacts are made through fenestrae in the thick basement membranes which separate the plasma membranes of the two cell types over most of their juxtaposed surfaces. This study was initiated to determine if there was any change in the number of pericyte-endothelial cell contact regions in retinal or optic nerve capillaries of the galactose-fed rat model for polyol-related complications of diabetes. Sprague-Dawley rats were fed for 28 months a 50% galactose diet, with or without an aldose reductase inhibitor (tolrestat), or a normal diet. Electron micrographs of transected capillaries were taken from defined regions of the central retina and nearby portions of the optic nerve. The optic nerve capillaries showed no differences in the numbers of pericyte-endothelial cell contact regions nor in basement membrane thickness in the galactose-fed rats. In contrast, the retinal capillaries exhibited a 70% decrease in the numbers of contact regions and a 2.4-fold increase in basement membrane thickness in galactosemic rats. Both loss of cell contact regions and basement membrane thickening were prevented with tolrestat. The results are consistent with the proposed involvement of the polyol pathway in diabetic retinopathy and with the greater involvement of retinal versus optic nerve vessels in diabetic microangiopathy.