Two vaccines were investigated on mouse strains of the inbred line C57BL/6: live attenuated HSV-1 vaccine HSV-1 0ΔNLS and the subunit vaccine (HSV-2). Immunization was carried out by prime-boost vaccination.
The acute and long-term protection was investigated by sample collection from the trigeminal ganglion. The research group found that the B- and T-cells play a decisive role in the success of the vaccination. Only the vaccine HSV-1 0ΔNLS was able to counteract a neuroinvasion by HSV (source 1). Today's article deals with a scientific study that gives hope for axon regeneration to patients who have suffered a trauma of the optic nerve. Read more in the following text (source 2).
Currently, the loss of function in neurodegenerative or traumatic diseases of the nervous system represents a major problem due to the limited regeneration possibilities. So far, the patients concerned have had little hope of improving their health situation. Optical damage caused by glaucoma or trauma is usually accompanied by a loss of retinal ganglion cells. This is due to axotomy induced cell apoptosis. But not only optic nerve trauma can result in axon degeneration with consecutive loss of function. Neurodegenerative diseases also steal the eyesight of the affected patient (source 2).
Up to now, the regeneration of axonal structures has been limited by the inhibition factors of the central nervous system. The inhibition factors involved initiate a signaling cascade resulting in the activation of cyclin-dependent kinase 5 (Cdk5) and glycogen synthase 3 beta (GSK3beta). Both enzymes lead to phosphorylation of the collapsin response mediator protein 2 (CRMP2). Phosphorylation by the Cdk5 at Ser522 inactivates CRMP2 in the next step. This allows subsequent phosphorylation by GSK3beta at Ser518, Thr514, and Thr509. This step results in the dreaded destabilization of the microtubules and leads to axonal degeneration. If there were a way to inhibit this signaling cascade, the optic nerve, and with it, the visual acuity, could be saved (source 2).
Today we get to know the research results of Kondo S. and his team. They have used a CRMP2 knock-in mouse strain to investigate how axonal regeneration can be made possible. What sounds like a dream from the future might soon be true. Every ophthalmologist can imagine in the wildest dreams what possibilities this would open up for the treatment of patients suffering from optic trauma or glaucomatous optic atrophy (source 2).
The CRMP2 knock-in mouse line prevents CRMP2 phosphorylation at Ser522. Interestingly, these special mice showed an increase in axonal regeneration after spinal cord injury. The research group wanted to use its experimental model to find out whether this increased axonal regeneration in CRMP2 knock-in mice also occurs after optic nerve trauma. Their recently published research results are groundbreaking as they are the first to report suppression of depolymerization of microtubules after optic trauma in CRMP2 knock-in mice (source 2).
CRMP2 knock-in mice also showed lower retinal cell loss after optic trauma compared to wild-type mice. The research group validated its results by determining the axonal regeneration marker GAP43. Compared to the wild type mouse group, CRMP2 knock-in mice showed a much higher GAP43 level 4 weeks after optic trauma. The research group concluded from this that inhibition of CRMP2 phosphorylation not only prevents axonal degeneration but also promotes axonal degeneration (source 2).
In the experimental model of Kondo S. and colleagues, inhibition of CRMP2 phosphorylation is associated with a neuroprotective effect. This result could soon become part of our clinical routine. These research results show us the pace at which therapy concepts, that may currently still appear futuristic, could shake our ophthalmological world for the better.
Sources:
1. Royer D. J. et al. (2019). Vaccine-induced antibodies target sequestered viral antigens to prevent ocular HSV-1 pathogenesis, preserve vision, and preempt productive neuronal infection. Mucosal Immunol. 2019 May;12(3):827-839.
2. Kondo S. et al. (2019). Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury. Scientific Reports.