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Kevin C. Chan, Jiang Li, Iris Y. Zhou, Phillis Kau, Kwok-fai So, Ed X. Wu; In vivo, Longitudinal MRI of Secondary Changes in the Uninjured Visual Pathway upon Partial Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2149.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a neurodegenerative disease involving the visual system in a topological manner. While the optic nerve (ON) head is a major site of injury, it is not clear if secondary degeneration occurs along the visual pathways that are not primarily injured in glaucoma. This study employed 3D T1-weighted Mn-enhanced MRI (MEMRI) at 7 Tesla to evaluate the uninjured nerves in the retinocollicular pathway longitudinally in an experimental model of partial ON injury.
The superior region of the right intraorbital ON in 10 adult Sprague-Dawley rats was partially transected at about 2mm from the eye. One and 6 weeks after surgery, MnCl2 solution (50mM, 3μL) was injected intravitreally into both eyes of the same animals. MEMRI was performed 1 day after Mn2+ administration. Throughout the experiments, the left ON was not transected and the visual pathway projected from left eye to right visual brain served as an internal control. After MRI experiments at Week 6, 4 rats were randomly chosen for histology using toluidine blue staining.
At both Week 1 and Week 6, the right vitreous and retina, and the right ON exhibited significantly higher and lower signal intensities respectively than the contralateral eye (paired t-tests, p<0.05). In addition, a consistent hypointensity by about 28% was observed in left lateral superior colliculus (SC) relative to right lateral SC (paired t-tests, p<0.001). The left medial SC had a reduced signal intensity by 11% compared to right medial SC at Week 1 (paired t-test, p<0.001). Such reduction further increased to 16% at Week 6 (paired t-test, p<0.01). Histology confirmed degeneration in both superior and inferior ON, with the superior ON showng more pronounced myelin debris formation and atrophy.
As more than 90% of rat ON fibers cross to the contralateral hemisphere at the optic chiasm, the consistent hypointensity in left lateral SC at Week 1 and Week 6 reflected the primary loss of topological connections and Mn2+ anterograde transport from right superior retina and ON. The slightly weaker enhancement in left medial SC at Week 1 might be partly due to reduced Mn2+ transport upon spreading of oxidative stress through the inferior retina early after partial ON injury, whereas the increased signal reduction in left medial SC at Week 6 might indicate secondary loss of retinal ganglion cells and axons projecting through the uninjured, inferior ON. The current results demonstrated the primary and secondary degenerative events along the visual pathways in vivo after partial ON injury. Future MEMRI studies are envisioned that measure the integrity of topological connections longitudinally upon pharmacologic interventions against secondary degeneration.
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