The loss of mural cells from capillary walls is the earliest histopathological lesion reported in diabetic retinas. Like several other diabetic complications, this lesion appears to be related to aldose reductase activity. Mural cells were cultured from capillaries of human retinas. Verification that contaminating cells had been removed was made on the basis of the mural cell's distinctive appearance in culture, inability to internalize acetylated-low-density lipoprotein, and immunoreactivity for muscle actin. Using pure cultures of human mural cells, the presence of aldose reductase was demonstrated immunohistochemically with antibodies directed against human placental aldose reductase, and aldose reductase activity was shown biochemically by monitoring the accumulation of xylitol in cells incubated with 30 mM xylose. Bovine and canine as well as human mural cells and endothelial cells from retinal capillaries have been grown in cell culture so that the role of aldose reductase in alterations of cell structure and function in the diabetic state could be studied under chemically defined conditions. Aldose reductase inhibitors are useful for studies of the possible prevention of diabetic retinopathy.
