Search

Background: The composition of gut microbiota plays a pivotal role in priming the immune system and thus impacts autoimmune diseases. Data on the effects of gut bacteria eradication via systemic antibiotics on immune neuropathies are currently lacking. This study therefore assessed the effects of antibiotics-induced gut microbiota alterations on the severity of experimental autoimmune neuritis (EAN), a rat model of Guillain-Barré Syndrome (GBS). Myelin P0 peptide 180–199 (P0 180–199)-induced EAN severity was compared between adult Lewis rats (12 weeks old) that received drinking water with or without antibiotics (colistin, metronidazole, vancomycin) and healthy rats, beginning antibiotics treatment immediately after immunization (day 0), and continuing treatment for 14 consecutive days. Neuropathy severity was assessed via a modified clinical score, and then related to gut microbiota alterations observed after fecal 16S rRNA gene sequencing at baseline and after EAN induction. Effectors of gut mucosal and endoneurial immunity were assessed via immunostaining. EAN rats showed increased gut mucosal permeability alongside increased mucosal CD8+ T cells compared to healthy controls. Antibiotics treatment alleviated clinical EAN severity and reduced endoneurial T cell infiltration, decreased gut mucosal CD8+ T cells and increased gut bacteria that may be associated with anti-inflammatory mechanisms, like Lactobacillus or Parasutterella. Our findings point out a relation between gut mucosal immunity and the pathogenesis of EAN, and indicate that antibiotics-induced intestinal immunomodulation might be a therapeutic approach to alleviate autoimmunity in immune neuropathies. Further studies are warranted to evaluate the clinical transferability of these findings to patients with GBS. [ABSTRACT FROM AUTHOR]

Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759). Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP. [ABSTRACT FROM AUTHOR]

Could symptom overlap of COVID-19 and Guillain-Barré syndrome mask an epidemiological association? In our case series, regarding a certain clinical amelioration of all patients after IVIg infusion, COVID-19 related GBS appears more likely than a direct infection of peripheral nerves with COVID-19. Dear Sirs, Whether COVID-19 can trigger Guillain-Barré syndrome (GBS) is currently controversially discussed. [Extracted from the article]

Intravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barré syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune complex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodies and IVIg or anti-ganglioside autoantibodies alone. Subsequently IgG dimer formation was assessed by high performance liquid chromatography (HPLC) and enzyme- linked immunosorbent assay (ELISA). In addition, IgG dimer formation was measured in sera of eight GBS patients who were treated with IVIg. In mice, a significant increase of dimeric IgG after administration of anti-ganglioside antibodies and IVIg could be observed. Re-monomerized IgG dimers showed immunoreactivity against gangliosides and serum immunoreactivity was significantly reduced after IVIg infusion. Likewise also in GBS patients, IgG dimer formation could be detected after IVIg treatment. Our data indicate that dimeric IgG immune complexes contain anti-idiotypic antibodies and provide proof of concept that IVIg treatment in GBS results in measurable amounts of IgG dimers. Larger patient cohorts are needed to evaluate serum IgG dimer increase as a possible marker for treatment response in GBS. [ABSTRACT FROM AUTHOR]

Transplantation of stem or progenitor cells is an attractive new approach for treating neurodegenerative conditions of the central nervous system, which aims to protect or replace neurons and improve function. Proof of principle has already been shown in the retina that photoreceptors may be replaced by transplantation of neural progenitor cells. However, the task of retinal ganglion cell replacement is much more complex, as new cells will need to establish complex connections within the retina and also extend axons to precise targets in the brain. Although progress has been made in this field, it is likely that neuroprotective clinical applications will be established more quickly. Our laboratory has focused on the intraocular transplantation of cells to treat inner retinal disease, either by neuronal replacement or neuroprotection of existing cells. We have investigated the efficacy and effects of transplanting a variety of cell types, including human Müller stem cells (MIO-M1), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs) in a rat model of experimentally induced glaucoma. We also have developed and characterized a novel in vitro organotypic retinal explant culture system for exploring the methods of enhancing the efficacy of cell transplantation for the inner retina. In this review, we discuss the potentially beneficial effects of intraocular cell injections, identify current shortcomings of retinal stem cell therapy, and suggest directions for future research. [ABSTRACT FROM AUTHOR]

Aim To quantify ciliary body position variability in glaucoma patients in order to determine if scleral transillumination should be used routinely to guide contact probe placement during cyclodestructive procedures.Method This was a prospective experimental study with human subjects. One hundred consecutive glaucoma patients attending a glaucoma clinic were recruited between June and November 2006. A fibre optic light source was used to identify ciliary body position by transscleral transillumination. The distance between the ciliary body and corneoscleral limbus was measured in the superior, temporal, inferior, and nasal quadrants of both eyes using surgical callipers.Results The anterior boundary of the ciliary body was located 1.5–5 mm posterior to the corneoscleral limbus. The ciliary body was located significantly more posteriorly in the superior and inferior quadrants compared to the nasal and temporal quadrants. (P<0.001). Ciliary body position was significantly correlated with the mean sphere of the refractive error in phakic patients (r2=0.052; P=0.047). The ciliary body tended to be located most posteriorly in myopic eyes.Conclusions The distance between the corneoscleral limbus and the ciliary body as identified by transillumination varies significantly in different quadrants of the eye. Considerable variability was also observed between different patients with glaucoma. Ciliary body transillumination on patients undergoing cyclodestructive procedures may have implications for optimal probe placement and therapeutic outcome.Eye (2008) 22, 1499–1503; doi:10.1038/eye.2008.79; published online 21 March 2008 [ABSTRACT FROM AUTHOR]

There is considerable interest in the effects of silica on human health in contrast to prior research which focused solely on the toxic effects of inhaled crystalline silica. However, multiple forms of silica exist in nature and silicon, a component, is the second most prevalent element after oxygen. Silica has widespread industrial applications including use as a food additive, i.e., anti-caking agent, as a means to clarify beverages, control viscosity, as an anti-foaming agent, dough modifier, and as an excipient in drugs and vitamins. Chemically, silica is an oxide of silicon, viz., silicon dioxide, and is generally colorless to white and insoluble in water. When associated with metals or minerals the family of silicates is formed. There are several water soluble forms of silica referred collectively to as silicic acid (ortho, meta, di, and tri-silicates), which are present in surface and well water in the range of 1 - 100 mg/L. Orthosilicic acid is the form predominantly absorbed by humans and is found in numerous tissues including bone, tendons, aorta, liver and kidney. Compelling data suggest that silica is essential for health although no RDI has been established. However, deficiency induces deformities in skull and peripheral bones, poorly formed joints, reduced contents of cartilage, collagen, and disruption of mineral balance in the femur and vertebrae. Very little toxicity data exist regarding aqueous silica consumption due, in part, to the lack of anecdotal reports of toxicity and general presumption of safety. However, a few rodent studies have been conducted, which indicate a No Observed Adverse Effects Level (NOAEL) of 50,000 ppm (mg/L) for dietary silica. In conclusion, many forms of silica exist in nature and compelling data support myriad beneficial effects of silica in water. [ABSTRACT FROM AUTHOR]

PURPOSE:There has been recent interest in the potential use of gene therapy techniques to treat ocular disease. In this article, we consider the optic nerve diseases that are potentially most amenable to gene therapy. METHODS:We discuss the recent success of gene transfer experiments in animal models of glaucoma, optic neuritis, Leber's hereditary optic neuropathy (LHON), and optic nerve transection, and we assess the possibility of using similar techniques to treat human disease in the future. RESULTS:We have achieved highly efficient transfection of retinal ganglion cells in a rat model of glaucoma following a single intravitreal injection of adeno-associated virus (AAV). In our model, we have found that AAV-mediated gene therapy with brain-derived neurotrophic factor has a significant neuroprotective effect compared to saline or control virus injections. Guy and co-workers have successfully used AAV-mediated gene therapy to replace the defective mitochondrial enzyme subunit in cells derived from human patients with LHON. Gene therapy techniques have also shown promise in animal models of optic neuritis and optic nerve trauma. CONCLUSIONS:Human diseases with single-gene defects such as LHON may soon be treated successfully by gene therapy, assuming that vectors continue to improve and are well tolerated in the human eye. Other optic nerve diseases such as glaucoma that do not have a single-gene defect may also benefit from gene therapy to enhance RGC survival. In all cases, the risks of treatment will need to be balanced against the potential benefits.Eye (2004) 18, 1049-1055. doi:10.1038/sj.eye.6701579 [ABSTRACT FROM AUTHOR]

The author reflects on the search for cell-transplantation-based therapies for glaucoma. It provides an overview on cell transplantation which is effective in protecting retinal ganglion cells and in treating many degenerative diseases such as glaucoma as well as the therapeutic mechanisms of cell replacement in many areas of medicine. The author suggests the need to determine the neuroprotective approach applicable for glaucoma and feasible to target cell transplantation.