Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve.
Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve.
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DOI：
10.1167/iovs.16-21362
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Palanker D
中科院分区：
文献类型：
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作者：
Brinton M;Kossler AL;Patel ZM;Loudin J;Franke M;Ta CN;Palanker D
电神经刺激可促进泪液分泌，可应用于干眼症的治疗。我们通过长期植入装置，评估刺激筛前神经对分泌泪液中水分、脂质和蛋白质含量的影响。
在13只新西兰白兔的鼻黏膜下植入神经刺激器。每天进行刺激（持续时间为75 - 875微秒、强度为2.3 - 2.8毫安的脉冲，以30 - 100赫兹的频率重复，持续3分钟），为期3周，以测量泪液量（泪液分泌试验）、渗透压（TearLab渗透压仪）、脂质（油红O染色法）和蛋白质（BCA检测法、质谱法）的变化。
在30至90赫兹频率范围内刺激筛前神经，泪液量增加了92%至133%（P≤0.01）。采用50%占空比（每6秒重复3秒刺激）进行调节治疗，泪液分泌量比持续刺激时又额外增加了23%（P≤0.01）。刺激结束后7分钟内，泪液分泌恢复到基线水平。泪膜渗透压降低了7毫渗摩尔/升，泪液脂质增加了24%至36%，蛋白质浓度增加了48%（P≤0.05）。泪腺蛋白质的相对丰度保持不变，而刺激后几种血清和角膜蛋白质减少（P≤0.05）。
电刺激筛前神经可增加泪液中的水分含量，降低泪液渗透压，增加脂质，并提高正常泪液蛋白质的浓度。使用鼻内刺激器进行的人体研究应在患有水液缺乏型和脂质缺乏型干眼症的患者中验证这些效果。
Electrical neurostimulation enhances tear secretion, and can be applied to treatment of dry eye disease. Using a chronic implant, we evaluate the effects of stimulating the anterior ethmoid nerve on the aqueous, lipid, and protein content of secreted tears. Neurostimulators were implanted beneath the nasal mucosa in 13 New Zealand white rabbits. Stimulations (2.3–2.8 mA pulses of 75–875 μs in duration repeated at 30–100 Hz for 3 minutes) were performed daily, for 3 weeks to measure changes in tear volume (Schirmer test), osmolarity (TearLab osmometer), lipid (Oil-Red-O staining), and protein (BCA assay, mass spectrometry). Stimulation of the anterior ethmoid nerve in the frequency range of 30 to 90 Hz increased tear volume by 92% to 133% (P ≤ 0.01). Modulating the treatment with 50% duty cycle (3 seconds of stimulation repeated every 6 seconds) increased tear secretion an additional 23% above continuous stimulation (P ≤ 0.01). Tear secretion returned to baseline levels within 7 minutes after stimulation ended. Tear film osmolarity decreased by 7 mOsmol/L, tear lipid increased by 24% to 36% and protein concentration increased by 48% (P ≤ 0.05). Relative abundance of the lacrimal gland proteins remained the same, while several serum and corneal proteins decreased with stimulation (P ≤ 0.05). Electrical stimulation of the anterior ethmoid nerve increased aqueous tear volume, reduced tear osmolarity, added lipid, and increased the concentration of normal tear proteins. Human studies with an intranasal stimulator should verify these effects in patients with aqueous- and lipid-deficient forms of dry eye disease.