Visual stimulation and brain-derived neurotrophic factor (BDNF) have protective effects in experimental autoimmune uveoretinitis
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39173995
DOI
10.1016/j.lfs.2024.122996
PII: S0024-3205(24)00586-1
Knihovny.cz E-zdroje
- Klíčová slova
- Brain-derived neurotrophic factor (BDNF), Experimental autoimmune uveoretinitis (EAU), Müller cells, Retina, Visual stimulation,
- MeSH
- autoimunitní nemoci * imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- retina metabolismus účinky léků MeSH
- retinitida * farmakoterapie prevence a kontrola imunologie MeSH
- uveitida * metabolismus farmakoterapie imunologie MeSH
- vazoaktivní intestinální peptid farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Bdnf protein, mouse MeSH Prohlížeč
- cytokiny MeSH
- mozkový neurotrofický faktor * MeSH
- vazoaktivní intestinální peptid MeSH
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.
Citace poskytuje Crossref.org