Abstract
Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.
Highlights
Diabetic retinopathy is a leading cause of acquired blindness from sequela such as edema, intraocular hemorrhage and fibrosis [1]
No apparent difference was observed in the cross-sectional diameter of the prechiasmatic optic nerve between experimental and control groups using scout T2-weighted magnetic resonance imaging (MRI) at 125μm x 125μm in-plane resolution
The STZ-induced diabetic rat model has been shown to cause abnormal visual function in the brain similar to diabetic patients [42]. While this model may lead to significant retinal thinning and inner retinal dysfunction few months after experimental induction [16,17,18, 43], recent histological studies have demonstrated significant axonal loss, myelin alterations, and astrocyte reactivity increase only in the intracranial but not intraorbital portion of the optic nerve after 6 weeks of STZ-induced experimental diabetes, with no substantial morphological alterations in the retina or superior colliculus [12,13,14]
Summary
Diabetic retinopathy is a leading cause of acquired blindness from sequela such as edema, intraocular hemorrhage and fibrosis [1]. Previous studies indicated that visual function may be impaired prior to physical exam findings of retinopathy in some diabetic patients [3,4,5,6,7,8]. Recent histological studies have demonstrated microstructural changes in the intracranial optic nerve of early experimental diabetes before substantial morphological alterations in the eye can be observed [12,13,14]. These findings suggest the early involvements of the brain’s visual system in diabetes. There is a need to investigate beyond the eye into the pathophysiological events in the brain’s visual system globally and more comprehensively, in order to better understand the exact mechanisms of visual impairments in diabetes and to guide more targeted vision preservation strategies
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