Microstructure abnormity in the optic nerve of type 1 diabetic rats revealed by diffusion tensor imaging study

Diabetic retinopathy (DR) is one of a major complication of type 1 diabetes mellitus (T1DM) and a leading cause of blindness. Evidence of animal study has shown that it is not only a microvasucular lesion of the eye, but also a neurodegeneration disease of the visual system. However, the in vivo imaging evidence of axonal degeneration in the diabetic optic nerve is scarce. Diffusion tensor imaging (DTI) technique has been proved to be an effective tool to track the integrity of the nerve fibers in the central nervous system. In this study, type 1 diabetes was induced by intraperitoneally injecting a single dose of streptozotocin (STZ) into Sprague-Dawley rats. DTI combined with histological assessments was carried out on the optic nerve to clarify the microstructural alterations underlying DTI indices changes at 4 weeks (4 w), 8 weeks (8 w) and 12 weeks (12 w) after STZ induction. The retinal changes were analyzed by pathological evaluations at 4 weeks (4 w) and 12 weeks (12 w) after STZ induction. DTI results showed significantly decreased mean diffusivity (MD) and axial diffusivity (Da) in diabetic optic nerve compared to controls at 12 w. Atrophy in diabetic nerves was monitored by high resolution T2-weighted images. Axonal degeneration without myelin loss of the optic nerve was confirmed by histological examination. Moreover, there are positive correlations between decreased diffusivities (MD and Da) in the optic nerve and reduced total axolemmal area. The diabetic rats showed intense glial activity since 4 w and thinning of the thickness in inner plexiform layer and nerve fiber layer at 12 w in the retina. In conclusion, DTI could in vivo monitor the progression of optic nerve degeneration in diabetes and the findings in our study would help supply axonal protection for DR in preclinical practice. DTI combined with histological assessments was carried out on the optic nerve in diabetic rats induced by streptozotocin to clarify the underlying microstructural alterations. Our study revealed the decreased diffusivities (MD and Da) detected by DTI were significantly correlated with the reduced total axolemmal area of optic nerve in diabetic rats. Diffusion metrics could be utilized to monitor the progressive axonal injury and assess the outcome for axonal protective therapies to prevent vision loss in diabetes. [Display omitted]