Retinal ganglion cell loss induced by acute optic neuritis in a relapsing model of multiple sclerosis

Abstract

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are marked by inflammatory demyelinating lesions throughout the central nervous system, including optic nerve. Neuronal loss also occurs in MS and EAE lesions, but it is not known whether neuronal loss occurs secondary to inflammation, or as a primary process. In the current study, the relationship of inflammation to retinal ganglion cell (RGC) loss during acute optic neuritis is examined. RGCs were labelled with Flourogold, and EAE was induced in SJL/J mice by immunization with proteolipid protein peptide 139-151 (PLP). At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltrates. No optic neuritis was detected prior to day 9 following immunization. Incidence of optic neuritis was 30% at day 9 and increased to over 70% by day 11, remaining high through day 18. In contrast, no RGC loss was detected in eyes with optic neuritis until day 14. A 43.1% reduction in RGC numbers at day 14 increased to 50.8% by day 18. No RGC loss occurred in eyes without optic neuritis. The fact that inflammation precedes RGC loss suggests that neuronal loss during optic neuritis occurs secondary to the inflammatory process.

Anatomical and functional retinal changes in multiple sclerosis

“…In the previous study, Shindler et al 1,2 demonstrated the progressive apoptosis of retinal ganglion cells after an acute episode of ON in murine models. 1,2 On the other hand, in 2011, Quinn et al 3 demonstrated the apoptosis of retinal ganglion cells also in the absence of acute inflammation of optic nerve after induction of autoimmune encephalomyelitis in the murine model; the authors suggested that it could be leaked to a specific genetic pattern or to the oxidative stress.…”

“…Along with the inflammatory processes, MS is characterized by a wide neurodegeneration, with axonal loss and neuronal rarefaction. [1][2][3][4][5][6] Acute optic neuritis (ON) is also a common feature of MS and it is the first clinical manifestation in~20% of patients affected by MS. 1,2 Spectral-domain optical coherence tomography (OCT) offers a unique opportunity for sensitive monitoring of anatomical changes of axonal and neuronal loss. 7,8 The objective of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with MS. We also investigated the correlation between SD-OCT structural changes and functional changes in terms of visual acuity and macular sensitivity, investigated with visual fields (VFs) and microperimetry (MP).…”

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

“…79 Various stimuli, like high intraocular pressure (IOP), blockage of axonal flow, and retinal ischemia may cause cellular damage in the retina. 80 Glaucoma, 81 ischemia, 82 age-related macular degeneration, 83 diabetic retinopathy, 84 and optic neuritis 85 are the potential contributors to retinal ganglion cells (RGCs) neurodegeneration and subsequent loss. It has been studied that survival of RGCs was enhanced by BDNF in vitro.…”

Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis

“…Several experimental optic neuritis models have been reported, including optic neuritis in relapsing-remitting EAE (Potter and Bigazzi, 1992;Shindler et al, 2006), chronic EAE (Meyer et al, 2001;Shao et al, 2004;Guyton et al, 2005;Qi et al, 2007a), and isolated optic neuritis in myelin oligodendrocyte glycoprotein (MOG)-specific T cell transgenic mice (Bettelli et al, 2003;Guan et al, 2006). We previously found that two-thirds of eyes from relapsing-remitting EAE mice develop optic neuritis by day 11 after immunization, but significant RGC loss is not detected until day 14 , suggesting that RGC loss occurs secondary to inflammation.…”