Patterns of retrograde axonal degeneration in the visual system

Abstract

Conclusive evidence for existence of acquired retrograde axonal degeneration that is truly trans-synaptic (RTD) has not yet been provided for the human visual system. Convincing data rely on experimental data of lesions to the posterior visual pathways. This study aimed to overcome the limitations of previous human studies, namely pathology to the anterior visual pathways and neurodegenerative co-morbidity. In this prospective, longitudinal cohort retinal optical coherence tomography scans were acquired before and after elective partial temporal lobe resection in 25 patients for intractable epilepsy. Newly developed region of interest-specific, retinotopic areas substantially improved on conventional reported early treatment diabetic retinopathy study (ETDRS) grid-based optical coherence tomography data. Significant inner retinal layer atrophy separated patients with normal visual fields from those who developed a visual field defect. Acquired RTD affected the retinal nerve fibre layer, ganglion cell and inner plexiform layer and stopped at the level of the inner nuclear layer. There were significant correlations between the resected brain tissue volume and the ganglion cell layer region of interest (R = −0.78, P < 0.0001) and ganglion cell inner plexiform layer region of interest (R = −0.65, P = 0.0007). In one patient, damage to the anterior visual pathway resulted in occurrence of microcystic macular oedema as recognized from experimental data. In the remaining 24 patients with true RTD, atrophy rates in the first 3 months were strongly correlated with time from surgery for the ganglion cell layer region of interest (R = −0.74, P < 0.0001) and the ganglion cell inner plexiform layer region of interest (R = −0.51, P < 0.0001). The different time course of atrophy rates observed relate to brain tissue volume resection and suggest that three distinct patterns of retrograde axonal degeneration exist: (i) direct retrograde axonal degeneration; (ii) rapid and self-terminating RTD; and (iii) prolonged RTD representing a ‘penumbra’, which slowly succumbs to molecularly governed spatial cellular stoichiometric relationships. We speculate that the latter could be a promising target for neuroprotection.

Retinal inter-eye difference and atrophy progression in multiple sclerosis diagnostics

“…Presently this is still a very labour and time consuming manual approach. 28 The atrophy rate of the mGCIPL was similar in our MS group and the HC group. One reason for this could be the relatively long disease duration of the patients with MS.…”

Progression of Visual Pathway Degeneration in Primary Open-Angle Glaucoma: A Longitudinal Study

“…Identifying the previously mentioned "trans-synaptic lag effect" in POAG could also prove to be beneficial to glaucoma treatment in the future. By further studying this effect and identifying its time frame more precisely, viable post-geniculate neurons corresponding to degenerated pre-geniculate neurons could be salvaged before they succumb to trans-synaptic degeneration A similar argument related to retrograde transsynaptic degeneration following injury to the post-geniculate pathways has been presented by de Vries-Knoppert and colleagues (de Vries-Knoppert et al, 2019). Such preventative measures could become critical in the context of the development of RGC transplantation efforts.…”

Homonymous visual field defect and retinal thinning after occipital stroke

“…Reduced GCIPL presents in the form of atypical diffuse or focal incongruent thinning, and/or characteristic homonymous quadrant‐ or hemi‐GCIPL thinning. Atypical GCIPL thinning has also been observed in different disease groups including congenital damages, multiple sclerosis (MS) plaques, surgical resection of Meyer's loop/temporal lobe, and tumors in the retrochiasmal pathways (de Vries‐knoppert et al., 2019 ; Gabilondo et al., 2014 ). In addition, atypical GCIPL thinning can occur in eye disorders such as glaucoma and retinopathy of different pathologies.…”