摘要
背景:动物模型在视网膜变性(RD)的病因和治疗研究中起着至关重要的作用。 目的:建立一种无严重全身副作用的猕猴RD模型。 方法:采用玻璃体内和静脉注射碘酸钠(SI)对食蟹猴和斯普拉格-达利大鼠进行治疗。采用视网膜电图(ERG)、荧光素眼底血管造影(FFA)、光学相干断层扫描(OCT)和视网膜形态检查等方法评价视网膜功能和结构。对 ARPE-19细胞进行SI处理,以评估细胞活力和形态。谷胱甘肽(GSH)给药硅处理的培养细胞和大鼠进行机械研究。 结果:静脉注射SI对猴子的致死性和视觉功能的自发恢复均不能诱导RD。然而,玻璃体内注射SI导致猴子和大鼠的视网膜损伤非常迅速和严重。在大鼠和猴子体内测试不同剂量的SI,并计算出适合模型的SI剂量。谷胱甘肽部分缓解了硅处理视网膜的氧化损伤。适当剂量的玻璃体腔注射和静脉注射谷胱甘肽可产生中度亚急性呼吸窘迫综合征。 结论:采用玻璃体腔注射法建立了食蟹猴的RD模型。该模型的主要优点是可以避免致命的SI副作用,结构和功能变化与RD患者相似,尽管模型中的RD发展太快,而且更严重。适当剂量的SI加上全身性GSH可产生延迟和中度的RD;这种延长的治疗时间允许为RD开发新的治疗方法,如基因或干细胞疗法。
关键词: 视网膜变性,动物模型,玻璃体内注射,谷胱甘肽,碘酸钠,治疗。
Current Molecular Medicine
Title:Establishment of Retinal Degeneration Model in Rat and Monkey by Intravitreal Injection of Sodium Iodate
Volume: 18 Issue: 6
关键词: 视网膜变性,动物模型,玻璃体内注射,谷胱甘肽,碘酸钠,治疗。
摘要: Background: Animal models play critical roles in studies of the etiology and therapy of retinal degeneration (RD).
Objective: To establish an RD model without severe systemic side effects in monkeys.
Methods: Cynomolgus monkeys and Sprague-Dawley rats were treated with intravenous and intravitreal sodium iodate (SI). Electroretinographic (ERG) recording, fluorescein fundus angiography (FFA), optical coherence tomography (OCT) and a retinal morphology examination were conducted to evaluate retinal function and structure. ARPE-19 cells were treated with SI to assess cell viability and morphology. Glutathione (GSH) was administered to SI-treated cultured cells and rats for mechanistic studies.
Results: Intravenous SI failed to induce RD in monkeys due to its lethal toxicity and the spontaneous recovery of visual function. However, intravitreal SI injection induced very rapid and severe retinal damage in both monkeys and rats. Different doses of SI were tested in both rats and monkeys, and the SI dose appropriate for the model was calculated. GSH partially rescued oxidative damage to SI-treated retinas. A combination of the appropriate dose of intravitreal SI and intravenous GSH generated moderate subacute RD.
Conclusions: An RD model was established in cynomolgus monkeys by intravitreal SI injection. The key advantages of this model are that lethal SI side effects can be avoided and that the structural and functional changes are similar to those in patients with RD, although the development of RD in the model is too rapid and more severe. An appropriate dose of SI plus systemic GSH generates delayed and moderate RD; this prolonged therapeutic window allows the development of new therapies, such as gene or stem cell-based therapy, for RD.
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Cite this article as:
Establishment of Retinal Degeneration Model in Rat and Monkey by Intravitreal Injection of Sodium Iodate, Current Molecular Medicine 2018; 18 (6) . https://dx.doi.org/10.2174/1566524018666181113104023
DOI https://dx.doi.org/10.2174/1566524018666181113104023 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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