Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 20 Staniford St., Boston, MA 02114, USA.
Exp Eye Res. 2013 Aug;113:148-50. doi: 10.1016/j.exer.2013.05.016. Epub 2013 Jun 14.
The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected non-invasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20 mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation.
角膜接受身体最密集的感觉神经支配，这些神经仅来自于小纤维伤害感受（疼痛感知）神经元。这些神经元与腿部皮肤中的神经元相似，腿部皮肤是用于诊断小纤维周围多发性神经病的神经诊断性皮肤活检的标准位置。许多癌症化疗药物会引起剂量相关的、治疗受限的、以感觉为主的多发性神经病。由于角膜神经支配可以非侵入性地检测到，因此它是皮肤活检测量的潜在替代生物标志物。因此，我们比较了接受神经毒性化疗的小鼠的后爪皮肤和角膜神经支配。给 C57/Bl6 小鼠给予紫杉醇（0、5、10 或 20mg/kg），并在濒死时对角膜和皮肤活检进行免疫标记，以显示和定量神经支配。两种组织均表现出剂量依赖性的、高度相关的（r=0.66）神经纤维损伤。这些发现表明，角膜神经的定量分析可能为皮肤周围神经支配提供有用的替代标志物。
