Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

Article

关键词: PHOTORECEPTOR CELL-DEATH;    TUMOR-NECROSIS-FACTOR;    PROLYL HYDROXYLASE INHIBITION;    NLRP3 INFLAMMASOME ACTIVATION;    APOPTOSIS-INDUCING FACTOR;    NF-KAPPA-B;    MICROGLIAL ACTIVATION;    POLY(ADP-RIBOSE) POLYMERASE;    OXIDATIVE STRESS;    MOUSE MODEL;   

DOI  :  10.1096/fj.202000044RR

来源: SCIE

【 摘 要 】

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by the progressive and irreversible loss of vision. We previously found that intraperitoneal administration of Adalimumab, a monoclonal anti-TNF alpha antibody, slowed down retinal degeneration in the murine model of RP, therd10mice. The aims of this study were to improve its neuroprotective effect and to deepen understanding of the molecular mechanisms involved in this effect. We analyzed (i) the in vitro effect of Adalimumab on the TNF alpha-mediated cell death in retinal cells; (ii) the effect of a single intravitreal injection of Adalimumab on retinal degeneration inrd10mice at postnatal day (P) 23. In vitro studies showed that TNF alpha induced caspase and poly ADP ribose polymerase (PARP) activation, downregulation of (kinase receptor-interacting protein 1) RIPK1 and upregulation of RIPK3 in retinal cells. Adalimumab reduced cell death probably through the inhibition of caspase 3 activation. In vivo studies suggested that PARP and NLRP3 inflammasome are mainly activated and to a lesser extent caspase-dependent mechanisms inrd10retinas at P23. Necroptosis seems to be inhibited by the downregulation of RIPK1. Adalimumab prevented from retinal degeneration without affecting caspase -dependent mechanisms but decreasing PARP activation, microglia activation as well as NLRP3 inflammasome.

【 授权许可】

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