Prolonged Retrobulbar Local Anesthesia of the Cornea Does Not Cause Keratopathy in Mice.

Prolonged Retrobulbar Local Anesthesia of the Cornea Does Not Cause Keratopathy in Mice.
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DOI:
10.1167/tvst.11.1.33
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发表时间:
2022-01-03
影响因子:
3
通讯作者:
Kohane DS
Kohane DS
中科院分区:
医学3区
文献类型:
--
作者:
Mehta M;Zhao C;Liu A;Innocent C;Kohane DS

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目前认为角膜的长期局部麻醉(PLA)会导致神经营养性角膜炎,并强烈建议不要使用。我们调查角膜本身的PLA是否会导致神经营养性角膜炎。在12只雌性白化病BALB/c小鼠中,通过球后注射聚合物前药(PGS-TTX)诱导角膜PLA,其中位点1钠通道阻断剂河豚毒素(TTX)从聚合物聚甘油癸二酸酯中缓慢释放。角膜麻醉的持续时间和深度由Cochet-Bonnet感觉计监测。采用裂隙灯检查(2%荧光素钠染料)、组织学、免疫组化(抗β III微管蛋白抗体)和共聚焦显微镜检查角膜神经密度、酶联免疫吸附测定角膜神经营养因子(P物质和神经激肽A)水平评估PLA对角膜的损伤。PLA也由局部阿米替林(80 mM)诱导,用作局部麻醉诱导的角膜损伤的阳性对照。经常进行眼部润滑。球后PGS-TTX导致完全角膜麻醉持续50.1 ± 3.6小时,阻滞完全消退的平均时间为55.1 ± 3.6小时,如果提供润滑,则无角膜病变。局部80 mM阿米替林诱导完全角膜麻醉24小时,并发生角膜病变。球后PGS-TTX组与正常角膜的组织学、角膜神经营养因子水平和角膜神经密度无差异。在没有局部毒性或角膜暴露的情况下,角膜本身的PLA不会引起角膜炎。角膜的PLA在急性和慢性疼痛性角膜病症中可能是非常有益的。
Prolonged local anesthesia (PLA) of the cornea is currently assumed to cause neurotrophic keratitis and is strongly discouraged. We investigate whether PLA of the cornea per se causes neurotrophic keratitis. PLA of the cornea was induced in 12 female albino BALB/c mice by retrobulbar injection of a polymeric prodrug (PGS-TTX) where the site 1 sodium channel blocker tetrodotoxin (TTX) was slowly released from the polymer polyglycerol sebacate. The duration and depth of corneal anesthesia was monitored by the Cochet-Bonnet esthesiometer. Corneal injury from PLA was assessed by slit lamp examination with 2% sodium fluorescein dye, histology, corneal nerve density by immunohistochemistry with anti-β III tubulin antibody and confocal microscopy, and corneal neurotrophin levels (substance P and neurokinin A) by an enzyme-linked immunosorbent assay. PLA was also induced by topical amitriptyline (80 mM), used as a positive control for local anesthetic-induced corneal injury. Frequent ocular lubrication was provided. Retrobulbar PGS-TTX resulted in complete corneal anesthesia lasting 50.1 ± 3.6 hours and mean time to complete resolution of block of 55.1 ± 3.6 hours with no keratopathy provided lubrication was provided. Topical 80 mM amitriptyline induced complete corneal anesthesia for 24 hours and developed keratopathy. There was no difference in the histology, levels of corneal neurotrophins, and corneal nerve density between the retrobulbar PGS-TTX group and normal cornea. In the absence of topical toxicity or corneal exposure, PLA of the cornea per se does not cause keratitis. PLA of the cornea could be highly beneficial in acute and chronic painful corneal conditions.
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