Reversal studies can preserve retinal capillary pericytes in galactose-fed dogs

Purpose. The selective degeneration of retinal capillary pericytes to form pericyte ghosts is considered a hallmark of diabetic retinopathy. Galactose-fed beagles have been observed to form diabetes-like microvascular changes which begin with the initial degeneration of pericyte and this degeneration has been shown to be arrested in a dose-dependent manner by aldose reductase inhibitors. To determine if the progression of pericyte degeneration can be reduced through the marked reduction of galactitol production after early retinal lesions have developed, galactose diet was removed after either the initial appearance of pericyte ghosts or microaneurysm formation. The subsequent progression of retinal changes over 29 months was then quantitively compared to retinal changes in remaining galactose-fed dogs. Methods. Ten control dogs were fed a normal diet, while 50 dogs were fed diet containing 30% galactose. The galactose diet was removed from 15 dogs after 24 months at which time pericyte ghosts had developed and another 15 dogs were removed after 31 months when microaneurysms had developed. Eighteen remained on galactose diet. Beginning at 24 months, 4-5 eyes from each experimental group and 2-3 eyes from the control group were enucleated at 6-month intervals. Isolated retinas were quantified as previously described (J. Ocular Pharmacol. 9: 257, 1993). These animal studies adhered to the ARVO Resolution on the Use of Animals in Research. Results. and Conclusion. Significant increases in the endothelium/ pericyte (E/P ratio) and decreases in pericyte density were observed with the duration of galactose-feeding. Although no reversal of retinal lesions occurred, the progression of retinal lesions in the galactose-fed groups was markedly reduced. This reduction mirrored the preservation of retinal capillary pericytes.