Immunosuppressive Treatment Can Alter Visual Performance in the Royal College of Surgeons Rat
Immunosuppressive Treatment Can Alter Visual Performance in the Royal College of Surgeons Rat
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DOI：
10.1089/jop.2015.0134
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发表时间：
2016-06-01
影响因子：
2.3
通讯作者：
Klassen, Henry
中科院分区：
文献类型：
--
作者：
Cooper, Ann E.;Cho, Jang-Hyeon;Klassen, Henry
目的：作为转化概念验证研究的一部分，免疫抑制经常用于增强异种移植的人类细胞的存活率。然而，这种治疗的潜在影响很容易被忽视。 方法：作为对营养不良的皇家外科学院 (RCS) 大鼠的黑眼变体进行基线测试的一部分，我们使用明场视网膜成像、荧光素血管造影和组织学记录了与 Long Evans 对照相比视网膜退行性变化的时间过程，并检查了免疫抑制对视觉功能的影响。大鼠不接受任何治疗，或口服环孢素 A 和注射地塞米松进行全身免疫抑制，随后在 P45 至 P180 的多个时间间隔内通过视运动反应测试和视网膜电图 (ERG) 进行功能评估。结果：在变性的早期阶段，免疫抑制的 RCS 动物在功能测试中表现出比年龄匹配的未治疗大鼠更差的表现，包括视运动阈值测试的空间敏锐度显着降低，b 波振幅显着降低关于暗视和明视 ERG。视网膜成像记录了 RCS 眼底退行性变化的进展情况，RCS 视网膜的组织学评估证实了外核层逐渐变薄。结论：对 RCS 大鼠施用环孢素 A 加地塞米松的标准方案，会导致明显的全身副作用，并在 P90 之前的时间点导致行为和电生理测试分数下降。功能障碍的根源尚未确定。这一发现对于解释使用这种常用翻译模型生成的数据具有重要意义。
Purpose: Immunosuppression is frequently employed to enhance survival of xenografted human cells as part of translational proof-of-concept studies. However, the potential effects of this treatment are easily overlooked.Methods: As part of baseline testing in the dark-eyed variant of the dystrophic Royal College of Surgeons (RCS) rat, we documented the time course of retinal degenerative changes versus Long Evans controls using bright field retinal imaging, fluorescein angiography, and histology and examined the impact of immunosuppression on visual function. Rats received either no treatment or systemic immunosuppression with oral cyclosporine A and injectable dexamethasone and subsequently underwent functional evaluation by optomotor response testing and electroretinography (ERG) at multiple intervals from P45 to P180.Results: Immunosuppressed RCS animals demonstrated poorer performance on functional tests than age-matched untreated rats during the earlier stages of degeneration, including significantly lower spatial acuities on optomotor threshold testing and significantly lower b-wave amplitudes on scotopic and photopic ERGs. Retinal imaging documented the progression of degenerative changes in the RCS fundus and histologic evaluation of the RCS retina confirmed progressive thinning of the outer nuclear layer.Conclusions: A standard regimen of cyclosporine A plus dexamethasone, administered to RCS rats, results in demonstrable systemic side effects and depressed scores on behavioral and electrophysiological testing at time points before P90. The source of the functional impairment was not identified. This finding has implications for the interpretation of data generated using this commonly used translational model.