Visual stimulation and brain-derived neurotrophic factor (BDNF) have protective effects in experimental autoimmune uveoretinitis.

Autor: Zloh M; Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic., Kutilek P; Department of Health Care and Population Protection, Faculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, Czech Republic., Hejda J; Department of Health Care and Population Protection, Faculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, Czech Republic., Fiserova I; Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic., Kubovciak J; Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic., Murakami M; Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Group of Quantum Immunology, Institute for Quantum Life Science, National Institute for Quantum and Radiological Science and Technology (QST), Chiba, Japan; Division of Molecular Neuroimmunology, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan., Stofkova A; Department of Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: andrea.stofkova@lf3.cuni.cz.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Oct 15; Vol. 355, pp. 122996. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1016/j.lfs.2024.122996
Abstrakt: Aims: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU).
Main Methods: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization).
Key Findings: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis).
Significance: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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