Background: Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).
Objectives: To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.
Methods: Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.
Results: Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.
Conclusions: These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.
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J Neurol Sci
December 2024
Toronto Eye Specialists and Surgeons, Toronto, Ontario, Canada; Department of Ophthalmology & Vision Science, University of Toronto, Toronto, Ontario, Canada; Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Canada. Electronic address:
Background: Few predictors of visual outcome after myelin oligodendrocyte glycoprotein (MOG) auto-antibody disease optic neuritis (ON) have been reliably elucidated. We evaluate whether between-study differences in ON neuroimaging regional enhancement features may underlie heterogeneity in reported visual prognosis.
Methods: PROSPERO (CRD42024580123).
Mol Neurobiol
December 2024
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10Th Ave, Rm 404, Miami, FL, 33136, USA.
The optic nerve contains retinal ganglion cell (RGC) axons and functions to transmit visual stimuli to the brain. Injury to the optic nerve from ischemia, trauma, or disease leads to retrograde axonal degeneration and subsequent RGC dysfunction and death, causing irreversible vision loss. Inflammatory responses to neurological damage and axonal injuries in the central nervous system (CNS) are typically harmful to neurons and prevent recovery.
View Article and Find Full Text PDFNat Commun
December 2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.
View Article and Find Full Text PDFPurpose: To observe the changes in peripapillary retinal nerve fiber layer (RNFL) thickness and peripapillary vessel densities (VD) in patients with rhegmatogenous retinal detachment (RRD) after scleral buckling (SB) by OCTA.
Methods: A total of 40 patients (40 eyes) with monocular RRD who underwent SB were included in the study, with the operated eyes (40 eyes) as the study group and the contralateral healthy eyes (40 eyes) as the control to analyse the changes in peripapillary RNFL thickness and VD before and after surgery. Data were analysed by paired samples -test or Wilcoxon signed rank sum test.
Acta Neuropathol Commun
December 2024
Department of Ophthalmology, UPMC Vision Institute, University of Pittsburgh School of Medicine, 1622 Locust Street, Pittsburgh, PA, 15219, USA.
Mammalian central nervous system (CNS) axons cannot spontaneously regenerate after injury, creating an unmet need to identify molecular regulators to promote axon regeneration and reduce the lasting impact of CNS injuries. While tubulin polymerization promoting protein family member 3 (Tppp3) is known to promote axon outgrowth in amphibians, its role in mammalian axon regeneration remains unknown. Here we investigated Tppp3 in retinal ganglion cells (RGCs) neuroprotection and axonal regeneration using an optic nerve crush (ONC) model in the rodent.
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