Diffusion Tensor Imaging Detects Retinal Ganglion Cell Axon Damage in the Mouse Model of Optic Nerve Crush

Abstract

Diffusion tensor imaging (DTI) measures the random motion of water molecules reflecting central nervous system tissue integrity and pathology. Glaucoma damages retinal ganglion cells (RGCs) and their axons. The authors hypothesized that DTI-derived axonal and myelin injury biomarkers may be used to detect early axonal damage and may be correlated with RGC loss in the mouse model of optic nerve crush (ONC). The progression of RGC axon degeneration was quantitatively assessed with DTI in vivo, corroborated with axon/myelin immunohistochemical staining and retrograde fluorogold labeling in mice after ONC. Decreased axial diffusivity (λ(‖)) and relative anisotropy (RA) of damaged axons were observed from 6 hours to 14 days, reflecting axonal injury. DTI detected axonal injury at 6 hours after ONC when SMI-31 did not detect axonal abnormality. Both decreased λ(‖), and SMI-31 identified axon damage at 3 days after ONC. Decreased λ(‖) correlated with reduced SMI-31-positive axon counts from 3 days after ONC. In contrast, the increased λ(⊥) was seen only in the distal segment of optic nerve whereas decreased myelin basic protein-positive axon counts were seen in all segments 3 days after ONC. The number of retrograde-labeled RGCs did not decline significantly until 7 days after ONC. There was a significant correlation between RGC loss and optic nerve axon damage. The authors demonstrated that in vivo DTI detected axonal injury earlier than SMI-31. Results suggest that in vivo DTI of optic nerve injury may be used as a noninvasive tool for assessing the pathogenesis of RGC axonal injury.