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Swarupa Kancherla, Ed Wu, Kevin C Chan; Distal visual pathway changes prior to retinopathy in streptozotocin-induced diabetes. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):598.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is a leading cause of acquired blindness. Recent studies indicated that visual function is impaired prior to diabetic retinopathy in diabetic patients. This suggested the early involvement of the distal visual pathway in the pathogenesis of diabetes. We assessed the integrity of the retina and visual pathway in early experimental diabetes using streptozotocin (STZ)-induced type 1 diabetic rats and in vivo MRI to determine if the distal visual pathway in the brain is altered before retina in diabetes.
Ten week old Sprague-Dawley rats (N=10) were randomized into 2 groups. Five underwent intraperitoneal injection of STZ at 65 mg/kg in 0.01M citric acid; The other 5 were injected with citric acid only and acted as control (CTRL). Diffusion tensor MRI (DTI) was performed 1 month later using a 7 Tesla MRI scanner. After DTI, chromium (Cr)-enhanced MRI was performed 1 day after intravitreal Cr(VI) injection into the left eye. Then, MnCl2 solution was intravitreally injected into the right eye, and manganese (Mn)-enhanced MRI was performed 1 day later. DTI parametric values including fractional anisotropy (FA), axial diffusivity (λ//) and radial diffusivity (λ┴) were extracted from prechiasmatic optic nerves. T1-weighted signal intensities were measured bilaterally in retina in Cr-enhanced MRI and subcortical visual nuclei in Mn-enhanced MRI. DTI parametric values and Cr and Mn enhancement were compared between STZ and CTRL using Students' t-tests.
STZ-induced diabetic rats had significantly smaller weight gain and higher blood glucose level than CTRL rats before MRI experiments. DTI revealed significant FA decrease and λ┴ increase in optic nerves of STZ compared to CTRL (p<0.05). There was no apparent difference between STZ and CTRL in Cr enhancement in the retina (131%±52% vs 119%±26%, p>0.05). Anterograde Mn transport as indicated by Mn enhancement in the lateral geniculate nucleus (41%±15% vs 55%±20%) and in the superior colliculus (60%±16% vs 62%±21%) was apparently unaffected in STZ compared to CTRL (p>0.05).
Our results suggest that STZ-induced type 1 diabetes first leads to structural changes in the distal optic nerve before MRI-detectable changes in retinal integrity and anterograde transport in retinocollicular and retinogeniculate pathways. Diffusion tensor imaging can detect the compromise in visual pathway integrity in early experimental diabetes.
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