0000000000414080
AUTHOR
Harald Von Pein
Chronic social defeat stress causes retinal vascular dysfunction
Abstract Purpose The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. Methods Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively.…
Correction: The genomic and clinical landscape of fetal akinesia
Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
How to treat tumefactive demyelinating disease?
Glioma-like inflammatory demyelinating lesions can be found in patients with pre-diagnosed multiple sclerosis, but they have also been described as an isolated disease entity. The initial diagnostic work-up usually includes a biopsy for histopathological analysis. However, even after unambiguous histopathologic classification, tumefactive lesions pose a therapeutic challenge. Until now, there have been no guidelines on how to treat patients with these rare and extreme lesion phenotypes. Here we report a patient with a relapsing unifocal tumefactive demyelinating lesion. The patient initially showed a good response to steroid treatment, with full clinical recovery. However, after relapse of…
Dynamics, alterations, and consequences of minimally invasive intraocular pressure elevation in rats.
PURPOSE: An important, yet not exclusive, aspect of primary open angle glaucoma is elevated intraocular pressure (IOP) profiles within fluctuations and pressure peaks. The study aimed at establishing minimally invasive methods for recurrent IOP elevation in rats to investigate the impact of IOP dynamics and pathomorphologic retinal alterations during and after IOP elevation. METHODS: Intraocular pressure was elevated unilaterally in Long Evans rats to a level of ≈35 mm Hg for 1 hour in a total of 30 manipulations within 6 weeks, by using two methods: (1) suction-cup oculopression and (2) loop-adjusted oculopression. Retinal thickness (RT) was measured via optical coherence tomography (OCT),…
Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.
Aim of the study. To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. Clinical rationale for the study. G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. Material and methods . A controlled traumatic right sciatic nerve lesion was set u…
Distribution of the hematopoietic growth factor G-CSF and its receptor in the adult human brain with specific reference to Alzheimer's disease
The granulocyte colony-stimulating factor (G-CSF), being a member of the hematopoietic growth factor family, is also critically involved in controlling proliferation and differentiation of neural stem cells. Treatment with G-CSF has been shown to result in substantial neuroprotective and neuroregenerative effects in various experimental models of acute and chronic diseases of the central nervous system. Although G-CSF has been tested in a clinical study for treatment of acute ischemic stroke, there is only fragmentary data on the distribution of this cytokine and its receptor in the human brain. Therefore, the present study was focused on the immunohistochemical analysis of the protein expr…
Murine genetic deficiency of neuronal nitric oxide synthase (nNOS-/-) and interstitial cells of Cajal (W/Wv): Implications for achalasia?
Background and aim Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice. Methods Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiqu…
The genomic and clinical landscape of fetal akinesia
International audience; Fetal akinesia has multiple clinical subtypes with over 160 gene associations, but the genetic etiology is not yet completely understood.Methods: In this study, 51 patients from 47 unrelated families were analyzed using next-generation sequencing (NGS) techniques aiming to decipher the genomic landscape of fetal akinesia (FA).Results: We have identified likely pathogenic gene variants in 37 cases and report 41 novel variants. Additionally, we report putative pathogenic variants in eight cases including nine novel variants. Our work identified 14 novel disease-gene associations for fetal akinesia: ADSSL1, ASAH1, ASPM, ATP2B3, EARS2, FBLN1, PRG4, PRICKLE1, ROR2, SETBP1…
Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.
BackgroundAntibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats.Methodology/principal findingsRats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The autoreactive antibody development against retina and optic nerve was examined throughout the study. The levels of autoreactive antibodies continuously in…
A new mitochondrial point mutation in the transfer RNALys gene associated with progressive external ophthalmoplegia with impaired respiratory regulation
Abstract We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA Lys in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a…