Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats.
Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats.
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DOI：
10.1016/j.exer.2016.06.010
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Pardue MT
中科院分区：
文献类型：
--
作者：
Hanif AM;Kim MK;Thomas JG;Ciavatta VT;Chrenek M;Hetling JR;Pardue MT
使用诸如视网膜下植入物和经角膜电刺激的方法，对眼睛的低水平电刺激已被证明对人类和动物受试者的视网膜变性具有神经保护作用。在这项研究中，我们研究了全眼电刺激（WES）在视网膜色素变性啮齿动物模型中的益处。用30分钟的低水平电刺激（4 μA，5 Hz; n = 10）或假刺激（Sham组; n = 15）处理具有P23 H-1视紫红质突变的转基因大鼠，每周两次，从4周龄至24周龄。每4周分别用视网膜电图和视动追踪评估视网膜和视功能。在最后时间点，摘除眼睛并进行组织学处理。单独的组群刺激一次，持续30分钟，并在刺激后1小时和24小时收获视网膜组织，用于生长因子和炎症和凋亡标志物的实时PCR检测。在处理后的所有时间点，WES处理的大鼠眼睛表现出比未处理的眼睛显著更高的空间频率阈值。通过ERG振荡电位（OPs）测量的视网膜内功能显示，与假手术眼相比，WES后8周和12周时OP振幅显著改善。此外，虽然P23 H-1大鼠的感光体节段和核厚度在治疗组之间没有变化，但在WES后20周，WES治疗的眼睛的视网膜神经节细胞核数量显著多于Sham眼睛。脑源性神经营养因子（BDNF），半胱天冬酶3，成纤维细胞生长因子2（FGF 2），谷氨酰胺合成酶（GS）的基因表达水平显着较高，在1小时，但不是24小时后WES治疗。我们的研究结果表明，WES对视网膜变性大鼠模型的视觉功能有有益的影响，并且后受体神经元可能对电刺激治疗特别敏感。
Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30 min of low-level electrical stimulation (4 μA at 5 Hz; n = 10) or sham stimulation (Sham group; n = 15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30 min, and retinal tissue harvested at 1 h and 24 h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1 h, but not 24 h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.