The natural history of primary progressive multiple sclerosis: insights from the German NeuroTransData registry.

Background: Primary progressive multiple sclerosis (PPMS) is characterised by gradual worsening of disability from symptom onset. Knowledge about the natural course of PPMS remains limited.

Methods: PPMS patients from the German NeuroTransData (NTD) MS registry with data from 56 outpatient practices were employed for retrospective cross-sectional and longitudinal analyses.

Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study.

Background: Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab.

Methods: CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years.

Design of a non-interventional post-marketing study to assess the long-term safety and effectiveness of ocrelizumab in German real world multiple sclerosis cohorts - the CONFIDENCE study protocol.

Background: Multiple sclerosis (MS) is a chronic disease that requires lifelong treatment. A highly effective drug not only for relapsing but also for progressive forms of MS with a favorable safety profile is needed to further improve overall patient outcomes. Ocrelizumab, a recombinant humanized monoclonal antibody that selectively targets CD20-expressing B-cells, is the first drug indicated for the treatment of adult patients with relapsing forms of MS (RMS) and primary progressive MS (PPMS).

Connexin57 is expressed in dendro-dendritic and axo-axonal gap junctions of mouse horizontal cells and its distribution is modulated by light.

Mouse horizontal cells are coupled by gap junctions composed of connexin57. These gap junctions are regulated by ambient light via multiple neuromodulators including dopamine. In order to analyze the distribution and structure of horizontal cell gap junctions in the mouse retina, and examine the effects of light adaptation on gap junction density, we developed antibodies that detect mouse retinal connexin57.

Ether-à-gogo-related gene (erg1) potassium channels shape the dark response of horizontal cells in the mammalian retina.

Postsynaptic to photoreceptors, horizontal cells face prolonged exposure to glutamate in the dark. Therefore, efficient hyperpolarizing mechanisms are crucial to keep horizontal cells within an operating range and to reduce glutamate-induced excitotoxicity. Combining electrophysiology, single-cell reverse transcriptase polymerase chain reaction, and immunocytochemistry, we found that horizontal cell bodies but not their axon terminals express the ether-à-gogo-related gene isoform 1 (erg1) K(+) channel.

Localization of heterotypic gap junctions composed of connexin45 and connexin36 in the rod pathway of the mouse retina.

The primary rod pathway in mammals contains gap junctions between AII amacrine cells and ON cone bipolar cells which relay the rod signal into the cone pathway under scotopic conditions. Two gap junctional proteins, connexin36 (Cx36) and connexin45 (Cx45), appear to play a pivotal role in this pathway because lack of either protein leads to an impairment of visual transmission under scotopic conditions. To investigate whether these connexins form heterotypic gap junctions between ON cone bipolar and AII amacrine cells, we used newly developed Cx45 antibodies and studied the cellular and subcellular distribution of this protein in the mouse retina.

The cytoplasmic domain of NrCAM binds to PDZ domains of synapse-associated proteins SAP90/PSD95 and SAP97.

NrCAM, a member of the L1 family of cell adhesion molecules, serves important functions during the development of the nervous system, e.g. in adhesion-dependent processes such as neurite outgrowth and axonal pathfinding.

Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation.

Migratory birds can use a magnetic compass for orientation during their migratory journeys covering thousands of kilometers. But how do they sense the reference direction provided by the Earth's magnetic field? Behavioral evidence and theoretical considerations have suggested that radical-pair processes in differently oriented, light-sensitive molecules of the retina could enable migratory birds to perceive the magnetic field as visual patterns. The cryptochromes (CRYs) have been suggested as the most likely candidate class of molecules, but do CRYs exist in the retina of migratory birds? Here, we show that at least one CRY1 and one CRY2 exist in the retina of migratory garden warblers and that garden-warbler CRY1 (gwCRY1) is cytosolic.

Characterization of retinoic acid neuromodulation in the carp retina.

Visual sensation in vertebrates starts with the isomerization of 11-cis retinaldehyde into all-trans retinaldehyde. Aldehyde dehydrogenases, present in the pigment epithelium and some retinal cells, convert all-trans retinaldehyde into all-trans retinoic acid (at-RA). Evidence in the retina and the hippocampus has accumulated, showing that at-RA, besides being a morphogenetic factor, also acts as a neuromodulator.