Počet záznamů: 1
Depletion of Retinal Dopaminergic Activity in a Mouse Model of Rod Dysfunction Exacerbates Experimental Autoimmune Uveoretinitis: A Role for the Gateway Reflex
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SYSNO ASEP 0555979 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Depletion of Retinal Dopaminergic Activity in a Mouse Model of Rod Dysfunction Exacerbates Experimental Autoimmune Uveoretinitis: A Role for the Gateway Reflex Tvůrce(i) Štofková, A. (CZ)
Zloh, M. (CZ)
Andreanska, D. (CZ)
Fišerová, I. (CZ)
Kubovčiak, Jan (UMG-J)
Hejda, J. (CZ)
Kutílek, P. (CZ)
Murakami, M. (JP)Celkový počet autorů 8 Číslo článku 453 Zdroj.dok. International Journal of Molecular Sciences. - : MDPI
Roč. 23, č. 1 (2022)Poč.str. 34 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova experimental autoimmune uveoretinitis ; gateway reflex ; dopamine ; Gnat1 ; night blindness ; rod-cone dystrophy ; blood-retinal barrier ; endothelial cells ; NF-kappa B ; stat3 Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000757140300035 DOI 10.3390/ijms23010453 Anotace 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 Gnat1(rd17) 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 Gnat1(rd17) 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-kappa B 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2023 Elektronická adresa https://www.mdpi.com/1422-0067/23/1/453
Počet záznamů: 1