Retinal capillary dilation: early diabetic-like retinopathy in the galactose-fed rat model

The purpose of this study was to determine whether capillary dilation is one of the earliest structural changes in the diabetic-like retinopathy of the galactose-fed rat model and thus may represent a stage where intervention treatment might still be effective. Weanling female Sprague-Dawley rats were randomized into 3 groups and fed Purina laboratory chow plus one of the following for 4 months: 50% starch (CONTROL); 50% D-galactose (Galactose); or 50% D-galactose with ARI-509 (25 mg/kg body wt/day) (Inhibitor). One eye from each of 5 rats per treatment group was processed for retinal vasculature wholemounts using elastase digestion, stained with a standard periodic-acid-Schiff reaction and counterstained with hematoxylin. Average capillary width, overall capillary density and total capillary length were measured, using computerized image analysis, within an arc-shaped area (4.4 mm2) of each vasculature surrounding, but separated from, the optic disc margin by approximately 0.7 mm. Galactose rats exhibited significant (p < 0.001) increases in capillary width (Mean +/- SEM: 7.56 +/- 0.07 microm) and density (42.78 +/- 0.37%) compared with CONTROL rats (6.68 +/- 0.11 microm and 37.18 +/- 0.30%, respectively). These increases were prevented with inhibitor treatment (6.58 +/- 0.16 microm and 35.88 +/- 0.97%, respectively). Capillary length remained unchanged at 4 months (

246.66 +/- 2.46 mm; Galactose: 250.75 +/- 1.26 mm; Inhibitor: 242.25 +/- 8.43 mm). Retinal capillary dilation, expressed as increased width and density, is one of the earliest detectable lesions in galactose-fed rats. In these rats, the lesion occurs as early as retinal capillary basement membrane thickening (RCBMT), one of the earliest reported changes in human diabetic retinopathy. Like RCBMT, capillary dilation can be prevented in rats with aldose reductase inhibitor treatment. Unlike RCBMT, capillary dilation could be clinically detectable and may be useful for the diagnosis of early retinopathy and for determining the timing of therapeutic intervention.