Dataset Information

Vision and Hyper-Responsiveness in Migraine.

ABSTRACT: : We investigated contrast processing in relation to visual comfort from coloured light in individuals with migraine. In Experiment 1, 24 individuals who experienced migraine with aura (MA), 15 migraine without aura (MO), and 23 healthy controls, identified which of four patterns, one in each quadrant, had the greatest contrast. Although there were no significant differences between groups, contrast discrimination was superior in the visual field affected by aura in all eight participants in whom the aura was consistently lateralised. In Experiment 2, 20 participants without aura and 20 controls selected comfortable light with a chromaticity close to the daylight (Planckian) locus, whilst 20 individuals with aura chose more strongly saturated colours, mostly distant from the locus. In Experiment 3, nine participants with consistently unilateral aura undertook the contrast discrimination task wearing (a) lenses that provided a comfortable colour of light and (b) grey lenses of similar transmission. With grey lenses, seven of the nine individuals with unilateral aura showed a superior performance in the affected field, as before. With lenses providing a comfortable colour, however, the performance was relatively poor for the nine individuals with unilateral aura, but not for the 10 controls. This was the case in both visual fields. The cortical hyper-responsiveness with which migraine is associated may improve the perception of contrast. The perception is poorer (and more normal) with ophthalmic lenses having a comfortable colour.

SUBMITTER: Aldrich A

PROVIDER: S-EPMC6969908 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Vision and Hyper-Responsiveness in Migraine.

Aldrich Amelia A Hibbard Paul P Wilkins Arnold A

Vision (Basel, Switzerland) 20191111 4

<b>:</b> We investigated contrast processing in relation to visual comfort from coloured light in individuals with migraine. In Experiment 1, 24 individuals who experienced migraine with aura (MA), 15 migraine without aura (MO), and 23 healthy controls, identified which of four patterns, one in each quadrant, had the greatest contrast. Although there were no significant differences between groups, contrast discrimination was superior in the visual field affected by aura in all eight participants ...[more]

PMID: 31735863

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Project description:IntroductionCeramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis.MethodsUtilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo. Intratracheal myriocin was administered alone or during house dust mite sensitization (HDM) of BALB/C mice and airway hyper-responsiveness (AHR) was evaluated by invasive plethysmography followed by bronchial lavage (BAL) cytology and cytokine quantification.ResultsMyriocin inhibits and HDM exposure activates de novo ceramide synthesis in bone marrow-derived dendritic cells. Mice receiving intratracheal myriocin developed a mild airway neutrophilic infiltrate without inducing a significant increase in AHR. CXCL1 was elevated in the BAL fluid of myriocin-treated mice while the neutrophilic chemotactic factors anaphylatoxin C5a, leukotriene B4, and IL-17 were unaffected. HDM treatment combined with myriocin led to a dramatic enhancement of AHR (63% increase over HDM alone, p < 0.001) and increased granulocyte pulmonary infiltrates versus HDM or myriocin alone. Elevated Th2 T cell counts and Th2 cytokines/chemokines (IL5, IL13, CCL17) were observed in mice treated with combined HDM/myriocin compared to HDM alone. Myriocin-treated pulmonary CD11c+ cells stimulated with HDM secreted significantly more CXCL1 than cells stimulated with HDM alone while HDM stimulated airway epithelial cells showed no change in CXCL1 secretion following myriocin treatment.ConclusionsIntratracheal myriocin, likely acting via ceramide synthesis inhibition, enhances allergen-induced airway inflammation, granulocyte and Th2 lymphocyte recruitment, and allergen-induced AHR. Sphingolipid pathways may represent novel targets for possible future anti-inflammatory asthma medications.

Project description:Selective stimulation of IL-4 receptor on smooth muscle induces airway hyper-responsiveness in mice. Abstract: Production of the cytokines IL-4 and IL-13 is increased in both human asthma and mouse asthma models and Stat6 activation by the common IL-4/IL-13R drives most mouse model pathophysiology, including airway hyperresponsiveness (AHR). However, the precise cellular mechanisms through which IL-4Rα induces AHR remain unclear. Overzealous bronchial smooth muscle constriction is thought to underlie AHR in human asthma, but the smooth muscle contribution to AHR has never been directly assessed. Furthermore, differences in mouse vs. human airway anatomy and observations that selective IL-13 stimulation of Stat6 in airway epithelium induces murine AHR raise questions about the importance of direct IL-4R effects on smooth muscle in murine asthma models and relevance of these models to human asthma. Using transgenic mice in which smooth muscle is the only cell type that expresses or fails to express IL-4Rα, we demonstrate that direct smooth muscle activation by IL-4, IL-13, or allergen is sufficient, but not necessary, to induce AHR and show that 5 genes known to promote smooth muscle migration, proliferation and contractility are activated by IL-13 in smooth muscle in vivo. These observations demonstrate that IL-4Rα promotes AHR through multiple mechanisms and provide a model for testing smooth muscle-directed asthma therapeutics. For the microarray aspect of of the study, there were three groups of mice: 1. IL4R gene knockout (KO) mice 2. WT mice 3. IL4R KO mice that were also transgenic for a gene construct that expressed IL4R under the control of the smooth muscle-specific promoter from the SMP8 gene All mice were subjected to intratracheal IL13 exposure for 7 days, and whole lung RNA was prepared for microarray analysis 24 hours after the last instillation. Per treatment and genotype: Two RNA pools were made from four mice each. These were labeled and hybridized to make a total of 6 microarrays. RNA was labeled with the standard Affymetrix 3' labeling protocol to make cDNA that was hybridized to Mouse MOE 430 plus 2.0 GeneChips. Gene transcripts were identified that differed in their relative expression as a function of IL4R expression on the smooth muscle cells.

Dataset Information

Vision and Hyper-Responsiveness in Migraine.

Publications

Vision and Hyper-Responsiveness in Migraine.

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