Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration.
Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration.
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DOI：
10.1038/srep11764
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发表时间：
2015-07-14
影响因子：
4.6
通讯作者：
Rodrigo R
中科院分区：
文献类型：
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作者：
Martínez-Fernández de la Cámara C;Hernández-Pinto AM;Olivares-González L;Cuevas-Martín C;Sánchez-Aragó M;Hervás D;Salom D;Cuezva JM;de la Rosa EJ;Millán JM;Rodrigo R
越来越多的证据表明，炎症参与视网膜色素变性（RP）的进展，无论是在患者和动物模型。本研究旨在研究阿达木单抗（一种单克隆抗TNF α抗体）对人常染色体隐性遗传RP小鼠模型（出生后第18天（P）的rd10小鼠）视网膜变性的影响。在我们的饲养条件下，rd10视网膜在P18时严重受损。通过对TUNEL阳性细胞数量进行评分，确定阿达木单抗可减少感光细胞死亡。此外，核聚（ADP）核糖（PAR）含量，PAR聚合酶（PARP）活性的间接措施，也减少治疗后。阻断TNFα可改善反应性胶质增生，表现为GFAP和IBA1免疫标记（分别为Müller细胞和小胶质细胞标记物）减少以及TNFα基因表达上调减少。阿达木单抗还通过恢复总抗氧化能力和超氧化物歧化酶活性改善抗氧化反应。最后，我们观察到阿达木单抗使rd 10小鼠视网膜的能量和代谢模式正常化。我们的研究表明，TNFα阻断可能是一种成功的治疗方法，以增加感光细胞的生存在RP的进展。还需要进一步的研究来表征其沿着疾病进展的作用。
Growing evidence suggests that inflammation is involved in the progression of retinitis pigmentosa (RP) both in patients and in animal models. The aim of this study was to investigate the effect of Adalimumab, a monoclonal anti-TNFα antibody, on retinal degeneration in a murine model of human autosomal recessive RP, the rd10 mice at postnatal day (P) 18. In our housing conditions, rd10 retinas were seriously damaged at P18. Adalimumab reduced photoreceptor cell death, as determined by scoring the number of TUNEL-positive cells. In addition, nuclear poly (ADP) ribose (PAR) content, an indirect measure of PAR polymerase (PARP) activity, was also reduced after treatment. The blockade of TNFα ameliorated reactive gliosis, as visualized by decreased GFAP and IBA1 immunolabelling (Müller cell and microglial markers, respectively) and decreased up-regulation of TNFα gene expression. Adalimumab also improved antioxidant response by restoring total antioxidant capacity and superoxide dismutase activity. Finally, we observed that Adalimumab normalized energetic and metabolic pattern in rd10 mouse retinas. Our study suggests that the TNFα blockade could be a successful therapeutic approach to increase photoreceptor survival during the progression of RP. Further studies are needed to characterize its effect along the progression of the disease.