EVALUATION OF RETINAL MICROCIRCULATORY ALTERATIONS IN THE GOTO-KAKIZAKI RAT - A SPONTANEOUS MODEL OF NON-INSULIN-DEPENDENT DIABETES

Purpose. To evaluate retinal microcirculation in the spontaneous diabe tic GK (Goto-Kakizaki) rat over an extended time. Methods. The dye-dil ution technique with scanning laser ophthalmoscope-based fluorescein a ngiography was used to evaluate retinal circulation in GK rats with di abetes of 1, 3, and 5 months' duration and in age-matched controls. Sc anning laser ophthalmoscope fluorescein angiograms were recorded after a 10-mu l bolus of 10% sodium fluorescein was injected into the tail vein, followed by a flush of 0.1 mi saline. Retinal mean circulation t imes (MCTs), vessel diameters, and retinal segmental blood flows (SBFs ) were determined using computer-assisted image analysis on a frame-by -frame basis. Results. The MCTs were significantly prolonged (P < 0.01 ) in the GK rat groups (2.60 +/- 0.31, 2.74 +/- 0.28, and 2.84 +/- 0.3 8 seconds at 1, 3, and 5 months' duration of diabetes, respectively) c ompared to the age-matched controls (1.94 +/- 0.20, 1.99 +/- 0.12, and 1.91 +/- 0.22 seconds, respectively). No significant differences were observed in the retinal arterial and venous diameters between groups at each time period. The SBFs were significantly reduced (P < 0.03) in the GK rat groups (12.0 +/- 1.5, 12.1 +/- 2.0, and 11.8 +/- 2.5 x 10( 2) mu m(2)/second at 1, 3, and 5 months' duration of diabetes, respect ively) compared to the controls (16.0 +/- 2.2, 16.7 +/- 1.8, and 17.2 +/- 2.5 x 10(2) mu m(2)/second, respectively). In either group, no sig nificant chang-es with growth were observed in MCT, vessel diameters, or SBF, although the MCTs in the GK rat group tended to lengthen, and arterial and venous diameters in the GI( rat group tended to increase with duration of diabetes. Goto-Kakizaki rats did not exhibit dense ca taracts, the retinal circulation could be observed, and morphologic ch anges of diabetic retinopathy did not develop throughout the experimen tal period. Conclusions. A significant prolongation in MCT and a signi ficant reduction in SBF appeared in GK rats at an early stage in diabe tes. This tendency continued until 5 months' duration of diabetes. The se results suggest that retinal circulatory abnormalities are found be fore observable retinopathy development in GK rats and that there may be some mechanism causing a reduction in SBF without changing major re tinal vessel diameters at an early stage in non-insulin-dependent diab etes mellitus (NIDDM). In addition, this study demonstrates that the G K rat will be a useful model of non-insulin-dependent diabetes mellitu s to evaluate retinal circulation over an extended time.