The gateway reflex is a mechanism by which neural inputs regulate chemokine expression at endothelial cell barriers, thereby establishing gateways for the invasion of autoreactive T cells into barrier-protected tissues. In this study, we hypothesized that rod photoreceptor dysfunction causes remodeling of retinal neural activity, which influences the blood-retinal barrier and the development of retinal inflammation. We evaluated this hypothesis using Gnat1rd17 mice, a model of night blindness with late-onset rod-cone dystrophy, and experimental autoimmune uveoretinitis (EAU). Retinal remodeling and its effect on EAU development were investigated by transcriptome profiling, target identification, and functional validation. We showed that Gnat1rd17 mice primarily underwent alterations in their retinal dopaminergic system, triggering the development of an exacerbated EAU, which was counteracted by dopamine replacement with L-DOPA administered either systemically or locally. Remarkably, dopamine acted on retinal endothelial cells to inhibit NF-κB and STAT3 activity and the expression of downstream target genes such as chemokines involved in T cell recruitment. These results suggest that rod-mediated dopamine release functions in a gateway reflex manner in the homeostatic control of immune cell entry into the retina, and the loss of retinal dopaminergic activity in conditions associated with rod dysfunction increases the susceptibility to autoimmune uveitis.

• Klíčová slova
• Gnat1, NF-κB, STAT3, blood–retinal barrier, dopamine, endothelial cells, experimental autoimmune uveoretinitis, gateway reflex, night blindness, rod-cone dystrophy,
• MeSH
• buněčné linie MeSH
• dopamin metabolismus   MeSH
• endoteliální buňky metabolismus   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• retina metabolismus   patologie   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• uveitida metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopamin MeSH
• NF-kappa B MeSH
• Stat3 protein, mouse MeSH Prohlížeč
• transkripční faktor STAT3 MeSH