Retinal Neurodegeneration in Type II Diabetic Otsuka Long-Evans Tokushima Fatty Rats

Abstract

We evaluated whether diabetes causes longitudinal thinning of retinal layers as a sign of retinal neurodegeneration in a type II diabetic animal model, the Otuska Long-Evans Tokushima fatty rats (OLETF), using spectral domain-optical coherence tomography (SD-OCT) and investigated the corresponding histology. Retinal thickness in OLETF and Long-Evans Tokushima Otsuka rats (LETO) was measured at 1300 μm from the center of the optic nerve head (ONH) at 12, 20, 28, and 36 weeks using SD-OCT. Total retinal thickness (TRT) was measured automatically by built-in software. The retinal nerve fiber layer (RNFL) and other layers' thicknesses were measured manually. At 36 weeks, eyes were processed for morphometric analysis and detection of apoptosis based on active caspase-3(+) and TUNEL(+) analysis. TRT was significantly thinner in OLETF at 28 and 36 weeks (236.26 ± 5.64 and 235.98 ± 5.42 μm, respectively) than in LETO (243.82 ± 7.36 and 239.58 ± 6.99 μm, respectively; P = 0.042 and P = 0.01). At 28 weeks, RNFL thickness was significantly lower in OLETF (21.52 ± 1.91 μm) than in LETO (24.75 ± 2.10 μm, P = 0.042). The change of TRT correlated significantly with change of RNFL thickness. At 36 weeks, OLETF (24.0 ± 3.1/cross-section) had significantly fewer ganglion cells than LETO (28.4 ± 6.7/cross-section, P = 0.028). Active caspase-3(+) and TUNEL(+) cells in RNFL were observed significantly more frequently in OLETF (6.8 ± 5.2/cross-section and 3.75 ± 0.96/cross-section, respectively) than in LETO (1.5 ± 2.3/cross-section, P = 0.008 and 1.0 ± 0.8/cross-section, P = 0.029, respectively). OLETF exhibited a significantly reduced TRT, especially RNFL thickness, based on SD-OCT. Further, histology revealed increased apoptosis and a decrease in the number of ganglion cells. These results suggest that retinal neurodegeneration occurs in type II diabetic OLETF.