Protective effects of transscleral sustained unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats
Protective effects of transscleral sustained unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats
复制标题
经巩膜持续乌诺前列酮递送对 S334ter 视紫红质突变大鼠视网膜变性的保护作用
DOI：
10.1002/jbm.b.33522
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Toshiaki Abe
中科院分区：
文献类型：
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作者：
Nobuhiro Nagai;Satoru Iwata;Kaori Sampei;Hideyuki Onami;Hirokazu Kaji;Matsuhiko Nishizawa;Toru Nakazawa;Yukihiko Mashima;Toshiaki Abe
已经表明，异丙基乌诺前列酮（UNO）在视网膜中具有有效的神经保护活性。评价持续经巩膜UNO递送至眼后段对光感受器变性的影响。通过基于聚二甲基硅氧烷模具的UV固化将UNO装载到由聚（乙二醇）二甲基丙烯酸酯制成的器械中。使用高效液相色谱法测量从这些装置扩散的UNO的量。在出生后21天将释放1.8 μg/天UNO的聚合物装置植入S334 ter大鼠的巩膜上，并将视网膜电图（ERG）与局部应用和安慰剂装置的ERG进行比较。通过组织学检查评估视网膜厚度。植入4周后，对标本进行Western印迹。ERG显示，与使用安慰剂器械或局部应用的结果相比，UNO负载器械可防止植入后2周和4周的ERG振幅降低。组织学检查显示，UNO加载装置防止视网膜厚度减少，标本的蛋白质印迹表明，UNO加载装置降低了ERK 1/2、磷酸化ERK 1/2和caspase-3的表达。提供持续UNO给药的装置保护视紫红质突变大鼠免于视网膜变性，因此，可能具有作为可持续给药方法以治疗视网膜色素变性的转化潜力。© 2015 Wiley Periodicals，Inc. J Biomed Mater Res Part B：Appl Biomater，104 B：1730-1737，2016。
It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold‐based UV‐curing. The amount of UNO diffusing from these devices was measured using high‐performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO‐loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO‐loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO‐loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase‐3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730–1737, 2016.