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Influence of pathogenic stimuli on Müller cell transfection by lipoplexes
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.ejpb.2020.03.009
Karen Peynshaert , Joke Devoldere , Frederik Philips , Fauve Vergauwe , Stefaan De Smedt , Katrien Remaut

Neuroprotection is a mutation-independent therapeutic strategy that seeks to enhance the survival of neuronal cell types through delivery of neuroprotective factors. The Müller cell, a retinal glial cell type appreciated for its unique morphology and neuroprotective functions, could be regarded as an ideal target for this strategy by functioning as a secretion platform within the retina following uptake of a transgene of our choice. In this in vitro study we aimed to investigate the capability of Müller cells to take up a standard liposomal vector (i.e. Lipofectamine 2000) and process its pDNA or mRNA cargo into the reporter GFP protein. By doing so, we found that mRNA outperformed pDNA in Müller cell transfection efficiency. Since neuroprotection is explored as a therapy for diabetic retinopathy and glaucoma, we furthermore examined the Müller cell’s lipoplex-induced transfection efficiency and cytotoxicity in stressful conditions linked to these diseases – i.e. hypoxia, hyperglycemia and oxidative stress. Interestingly, Müller cells were able of maintaining high GFP expression regardless of these noxious stimuli. In terms of lipoplex-induced toxicity, hyperglycemia seemed to have a protective effect while hypoxia and oxidative stress led to a slightly higher toxicity. In conclusion, our study indicates that mRNA-lipoplexes have potential in transfecting Müller cells in healthy as well as diseased conditions.



中文翻译:

致病性刺激对脂质复合物转染Müller细胞的影响

神经保护是一种与突变无关的治疗策略,旨在通过传递神经保护因子来提高神经元细胞类型的存活率。Müller细胞是一种视网膜胶质细胞类型,因其独特的形态和神经保护功能而备受赞誉,通过摄取我们选择的转基因,其在视网膜内起着分泌平台的作用,因此可以被视为该策略的理想靶标。在这个体外这项研究旨在研究Müller细胞吸收标准脂质体载体(即Lipofectamine 2000)并将其pDNA或mRNA货物加工成报告GFP蛋白的能力。通过这样做,我们发现在Müller细胞转染效率中,mRNA优于pDNA。由于探索了神经保护作用作为糖尿病性视网膜病和青光眼的治疗方法,因此我们进一步研究了在与这些疾病相关的应激条件下,即缺氧,高血糖和氧化应激,Müller细胞的脂质复合物诱导的转染效率和细胞毒性。有趣的是,无论这些有害刺激如何,Müller细胞都能够维持高GFP表达。就脂质复合物诱导的毒性而言,高血糖似乎具有保护作用,而低氧和氧化应激导致毒性稍高。结论,

更新日期:2020-03-12
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