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Progression of Anterograde Trans-Synaptic Degeneration in the Human Retina Is Modulated by Axonal Convergence and Divergence.

ABSTRACT: In the visual pathway of patients with multiple sclerosis (MS), the inner nuclear layer (INL) of the retina is a tight barrier for retrograde trans-synaptic degeneration. In this observational, retrospective cross-sectional study, segmented macular spectral domain optical coherence tomography (OCT) volume scans were reviewed to investigate if this observation also holds true for anterograde trans-synaptic degeneration. Significant thinning was found in all retinal layers in patients with outer retinal diseases compared with the healthy controls, while there was no significant attenuation of the outer retina in patients with MS. In contrast to the tight barrier function observed with retrograde trans-synaptic degeneration, the INL appears to be more permissive for the propagation of anterograde trans-synaptic degeneration. We speculate that this may be due to the size of the area affected and be explained by convergence and divergence of axons within the retinal layers. These findings are likely relevant to future restorative stem cell treatment of the outer retinal layers, as time may matter.

SUBMITTER: Panneman EL

PROVIDER: S-EPMC7053976 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Progression of Anterograde Trans-Synaptic Degeneration in the Human Retina Is Modulated by Axonal Convergence and Divergence.

Panneman E L EL Coric D D Tran L M D LMD de Vries-Knoppert W A E J WAEJ Petzold A A

Neuro-ophthalmology (Aeolus Press) 20190527 6

In the visual pathway of patients with multiple sclerosis (MS), the inner nuclear layer (INL) of the retina is a tight barrier for retrograde trans-synaptic degeneration. In this observational, retrospective cross-sectional study, segmented macular spectral domain optical coherence tomography (OCT) volume scans were reviewed to investigate if this observation also holds true for anterograde trans-synaptic degeneration. Significant thinning was found in all retinal layers in patients with outer r ...[more]

PMID: 32165897

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Project description:In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.

Dataset Information

Progression of Anterograde Trans-Synaptic Degeneration in the Human Retina Is Modulated by Axonal Convergence and Divergence.

Publications

Progression of Anterograde Trans-Synaptic Degeneration in the Human Retina Is Modulated by Axonal Convergence and Divergence.

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