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Timothy S. Kern, Jie Tang, Masakazu Mizutani, Renu A. Kowluru, Ram H. Nagaraj, Giulio Romeo, Francesca Podesta, Mara Lorenzi; Response of Capillary Cell Death to Aminoguanidine Predicts the Development of Retinopathy: Comparison of Diabetes and Galactosemia. Invest. Ophthalmol. Vis. Sci. 2000;41(12):3972-3978.
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purpose. To examine the relationship between early retinal capillary cell
apoptosis and late histologic lesions of diabetic retinopathy and to
compare the effects of aminoguanidine (AMG) on the retinopathies caused
by diabetes and galactose feeding.
methods. Rats with alloxan-induced diabetes and rats fed a 30% galactose diet
(known to induce diabetic-like retinopathy) were assigned randomly to
receive diet with (2.5 g/kg diet) or without AMG. After 6 to 8 months
of diabetes or galactosemia, retinal trypsin digests were prepared, and
capillary cell apoptosis was quantitated using the Tdt-mediated dUTP
nick-end labeling (TUNEL) reaction in association with morphologic
evidence of nuclear fragmentation. At 18 months duration, pericyte
ghosts and acellular capillaries were quantitated in the isolated
vasculature. Several advanced glycation end products (AGEs) were
measured at 4 months of study and at 18 months of study by established
methods to assess biochemical effects of AMG.
results. As expected, both diabetic and galactosemic rats showed increased
frequency of TUNEL-positive capillary cells at 6 to 8 months and
vascular lesions characteristic of retinopathy at 18 months. AMG
inhibited both the early apoptosis and late histopathology in the
diabetic rats, but neither of these abnormalities in the galactosemic
rats. In contrast to its preventative effect on retinopathy in the
diabetic rats, AMG showed no inhibitory effect on levels of hemoglobin
AGE, or tail collagen pentosidine, fluorescence, and thermal breaking
time. Diabetes of 4 months’ duration did not cause a detectable
increase in retinal levels of several AGEs.
conclusions. The frequency of early apoptosis in retinal microvascular cells
predicted the development of the histologic lesions of retinopathy in
diabetes as well as in galactosemia. The beneficial effect of AMG on
retinal lesions in diabetes is exerted on pathways that are either not
operative or are less important in galactosemia and that may not relate
to the accumulation of AGEs.
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