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首页> 外文期刊>Drug delivery. >Toward smart design of retinal drug carriers: a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface
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Toward smart design of retinal drug carriers: a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface

机译：迈向视网膜药物载体的智能设计：一种新型的牛视网膜外植体模型，用于研究玻璃体视网膜界面的屏障作用

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Abstract Retinal gene delivery via intravitreal injection is hampered by various physiological barriers present in the eye of which the vitreoretinal (VR) interface represents the most serious hurdle. In this study, we present a retinal explant model especially designed to study the role of this interface as a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, the developed model is bovine-derived and more importantly, keeps the vitreous attached to the retina at all times to guarantee an intact VR interface. After ex vivo intravitreal injection into the living retinal explant, the route of fluorescent carriers across the VR interface can be tracked. By applying two different imaging methods on this model, we discovered that the transfer through the VR barrier is size-dependent since 40?nm polystyrene particles are more easily taken up in the retina than 100 and 200?nm sized particles. In addition, we found that removing the vitreous, as commonly done for culture of conventional explants, leads to an overestimation of particle uptake, and conclude that the ultimate barrier to overcome for retinal uptake is undoubtedly the inner limiting membrane. Damaging this matrix resulted in a massive increase in particle transfer into the retina. In conclusion, we have developed a highly relevant ex vivo model that maximally mimics the human in vivo physiology which can be applied as a representative test set-up to assess the potential of promising drug delivery carriers to cross the VR interface.
机译：摘要玻璃体内注射使视网膜基因传递受到眼中存在的各种生理屏障的阻碍，其中玻璃体视网膜（VR）界面是最严重的障碍。在这项研究中，我们提出了一种视网膜外植体模型，专门设计用于研究该界面作为载体渗透到视网膜中的屏障的作用。与所有现有的外植体模型相反，已开发的模型是牛衍生的，更重要的是，它始终保持玻璃体附着在视网膜上，以确保完整的VR接口。在将玻璃体内注射入活体视网膜外植体后，可以追踪荧光载体跨VR接口的路径。通过在该模型上应用两种不同的成像方法，我们发现通过VR屏障的转移与尺寸有关，因为视网膜上40纳米的聚苯乙烯颗粒比100纳米和200纳米的颗粒更容易被视网膜吸收。此外，我们发现像常规外植体培养一样，去除玻璃体会导致对颗粒摄取的高估，并得出结论，克服视网膜摄取的最终障碍无疑是内在限制膜。损坏该基质导致颗粒大量转移到视网膜中。总之，我们已经开发了高度相关的离体模型，该模型最大程度地模拟了人类体内的生理学，可以用作代表性的测试装置，以评估有前途的药物输送载体穿越VR接口的潜力。

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