Optic neuritis (i.e. inflammation of the optic nerve at the back of the eye) is one of the most frequent presentations in MS. It can result in either semi-permanent or permanent visual loss. Attempts to aid visual recovery have been partially successful with the use of sodium channel blockers, but not with remyelination therapies, such as anti-LINGO.
This paper on retinal oxygen supply may be the answer to why a remyelination strategies may not work. Whilst sodium channel blockade strategies that protect neurones via the mechanism of reducing nitric oxide (NO) induced mitochondrial compromise may just work.
Here Kallab et al. demonstrate that there is reduced retinal (the area where the nerve fibre layer that processes visual information sits) oxygen extraction paralleled by a decrease in blood flow in the ON eye compared to the normal eye (see Figure below). Mitochondrial dysfunction that frequently occurs in ON is probably what leads to the reduction in oxygen extraction in the affected retina.
With these changes there is also a reduction in the density of blood vessels in the ON eye:
These eventual structural changes will make it difficult to deliver products to the area most needed without the accompanying blood supply. To make effective changes in the process, any treatment that is being tried as a treatment for ON will need to take place before this pruning of blood vessels starts. The alternative and my crazy suggestion is to use VEGF (vascular endothelial growth factor) – which is periodically given as an injection into the eye for a condition called macular degeneration to promote the growth of blood vessels; here to improve microvascular pruning before commencing a therapeutic trial for the ON.
Retinal Oxygen Metabolism and Haemodynamics in Patients With Multiple Sclerosis and History of Optic Neuritis
Martin Kallab , Nikolaus Hommer , Andreas Schlatter , Gabriel Bsteh , Patrick Altmann , Alina Popa-Cherecheanu , Martin Pfister , René M Werkmeister , Doreen Schmidl , Leopold Schmetterer , Gerhard Garhöfer
Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.