A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate
A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate
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DOI：
10.1167/iovs.16-19355
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发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
Fernandez, Eduardo
中科院分区：
文献类型：
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作者：
Mones, Jordi;Leiva, Marta;Fernandez, Eduardo
目的。目的采用光谱域光学相干断层扫描(SD-OCT)和免疫细胞化学方法，建立毒素诱导的选择性视网膜外层、视网膜色素上皮(RPE)和光感受器局限性萎缩的大动物模型。方法15头雄性和雌性健康约克夏猪在全身麻醉下单侧视网膜下递增剂量NaIO3。在所有动物中，通过23/38口径的视网膜下插管将0.1~0.2mLNaIO3注射到中心区的视网膜下间隙。对照组于术后1个月和2个月行SD-OCTs检查，分别于术后1、2个月处死猪，摘除眼球。结果：光谱域OCT和免疫组织化学显示，用0.01 mg/mL的视网膜下碘化钠治疗的猪的眼底镜下病变局限于视网膜外层。结论：本研究建立的猪视网膜损伤控制区域模型，边界清楚，有选择性地位于视网膜外层，显示了AMD的几个临床和组织学特征。因此，在研究旨在恢复视功能的新的再生疗法，如干细胞移植或光遗传学方面，它可能是一个有价值的工具。
PURPOSE. To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry.METHODS. Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.1 to 0.2 mL NaIO3 were injected into the subretinal space of the area centralis through a 23/38-gauge subretinal cannula. Control SD-OCTs were performed 1 and 2 months after the surgery, at which time pigs were euthanized and eyes enucleated. Globes were routinely processed for histologic and immunohistochemical evaluation.RESULTS. Spectral-domain OCT and immunohistochemistry revealed circumscribed and well demarcated funduscopic lesions, limited to the outer retinal layers in pigs treated with 0.01 mg/mL subretinal sodium iodate.CONCLUSIONS. The swine model of a controlled area of circumscribed retinal damage, with well-delimited borders, and selectively of the outer layers of the retina presented herein shows several clinical and histologic features of geographic atrophy in AMD. Therefore, it may represent a valuable tool in the investigation of new emerging regenerative therapies that aim to restore visual function, such as stem cell transplantation or optogenetics.