Vascular changes associated with early
diabetic retinopathy that include the selective degeneration of pericytes, the formation of
microaneurysms and acellular capillaries, and vessel dilation have been experimentally investigated in age- and sex-matched beagle dogs fed a 30%
galactose diet and treated with or without the
aldose reductase inhibitors
sorbinil and/or
M79175. Eyes from dogs in each group were periodically enucleated during a 36-month period and their
retinal capillaries were examined as
trypsin-digested flat preparations. These studies reveal that the destruction of
retinal pericytes to form pericyte ghosts is the earliest observable retinal vessel change occurring after 19 to 21 months of
galactose feeding. By 24 months, both an irregular distribution of endothelial cell nuclei near pericyte ghosts and the presence of acellular capillaries containing neither endothelial cells nor pericytes can be observed. This was followed by the histologic appearance of
microaneurysms after 27 months and the funduscopic appearance of intraretinal
hemorrhages after 33 months. Varicose enlargements of capillaries were also observed in the
trypsin-digested preparations from dogs fed
galactose for 33 to 36 months. All of these changes are linked to the initial
aldose reductase-associated destruction of pericytes. The onset and progression of these
retinal changes were retarded in a dose-dependent manner with
aldose reductase inhibitors.