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Manipulating ocular endothelial tight junctions: Applications in treatment of retinal disease pathology and ocular hypertension
Progress in Retinal and Eye Research ( IF 17.8 ) Pub Date : 2017-09-22 , DOI: 10.1016/j.preteyeres.2017.09.003
Matthew Campbell , Paul S. Cassidy , Jeffrey O'Callaghan , Darragh E. Crosbie , Pete Humphries

Protein levels of endothelial tight-junctions of the inner retinal microvasculature, together with those of Schlemm's canal, can be readily manipulated by RNA interference (RNAi), resulting in the paracellular clefts between such cells to be reversibly modulated. This facilitates access to the retina of systemically-deliverable low molecular weight, potentially therapeutic compounds, while also allowing potentially toxic material, for example, soluble Amyloid-β1-40, to be removed from the retina into the peripheral circulation. The technique has also been shown to be highly effective in alleviation of pathological cerebral oedema and we speculate that it may therefore have similar utility in the oedematous retina. Additionally, by manipulating endothelial tight-junctions of Schlemm's canal, inflow of aqueous humour from the trabecular meshwork into the Canal can be radically enhanced, suggesting a novel avenue for control of intraocular pressure. Here, we review the technology underlying this approach together with specific examples of clinical targets that are, or could be, amenable to this novel form of genetic intervention.



中文翻译:

操纵眼内皮上紧密连接:在视网膜疾病病理和高眼压的治疗中的应用

RNA干扰(RNAi)可以很容易地控制视网膜内微脉管系统内皮紧密连接的蛋白水平以及Schlemm管的蛋白水平,从而可逆地调节此类细胞之间的旁细胞cellular裂。这有利于进入系统可递送的低分子量潜在治疗化合物的视网膜,同时还允许将潜在有毒物质(例如可溶性淀粉样蛋白β1-40)从视网膜上清除到周围循环中。该技术还被证明在减轻病理性脑水肿方面非常有效,因此我们推测它在水肿性视网膜中可能具有相似的效用。此外,通过操纵Schlemm管的内皮紧密连接,房水从小梁网流入运河的现象可以得到根本性的增强,这为控制眼内压提供了一条新途径。在这里,我们回顾了这种方法的基础技术以及临床目标的具体实例,这些实例可以或可能适用于这种新型的基因干预形式。

更新日期:2017-09-22
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