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

To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). 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). 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). 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.

Zloh M ，Kutilek P ，Hejda J ，Fiserova I ，Kubovciak J ，Murakami M ，Stofkova A ... -  《-》

Prevention of experimental autoimmune uveoretinitis by vasoactive intestinal peptide.

Keino H ，Kezuka T ，Takeuchi M ，Yamakawa N ，Hattori T ，Usui M ... -  《archives of ophthalmology》

Mice lacking the IFN-gamma receptor or fyn develop severe experimental autoimmune uveoretinitis characterized by different immune responses.

Fukushima A ，Yamaguchi T ，Ishida W ，Fukata K ，Udaka K ，Ueno H ... -  《IMMUNOGENETICS》

The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice.

Chen J ，Vistica B ，Wiggert B ，Chan CC ，Gery I ... -  《OCULAR IMMUNOLOGY AND INFLAMMATION》

Protective effect of intravitreal injection of vasoactive intestinal peptide-loaded liposomes on experimental autoimmune uveoretinitis.

Camelo S ，Lajavardi L ，Bochot A ，Goldenberg B ，Naud MC ，Brunel N ，Lescure B ，Klein C ，Fattal E ，Behar-Cohen F ，de Kozak Y ... -  《-》