School of Optometry & Vision Science, University of New South Wales, Australia.
School of Optometry & Vision Science, University of New South Wales, Australia.
Ocul Surf. 2019 Oct;17(4):690-698. doi: 10.1016/j.jtos.2019.08.010. Epub 2019 Aug 30.
To explore the changes that occur in the concentrations of substance P (SP) and calcitonin gene-related peptide (CGRP) in tears as a result of corneal denervation and its association with diabetic peripheral neuropathy (DPN).
Sixty-three individuals with type 1 diabetes/type 2 diabetes (T1D/T2D) and 34 age-matched healthy controls underwent a detailed assessment of neuropathy using the Total Neuropathy Score (TNS). The concentration of SP and CGRP in tears was measured by enzyme-linked immunosorbent assay. The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fibre length, fibre density, branch density, total branch density, nerve fractal dimension and inferior whorl length were quantified.
In T1D, the median [IQR] concentration of SP in tears was significantly reduced in those with DPN, (130 [61-692]pg/mL) compared to both control subjects (763 [405-1555]pg/mL, P < 0.01) and in those without DPN (914 [339-1832]pg/mL, P = 0.01); the concentration of CGRP was not changed. In T2D, there was no difference in neuropeptides between participants with diabetes and controls, regardless of neuropathic status. In T1D and T2D, corneal nerve parameters were significantly different between those with DPN or without DPN and controls. A significant correlation was noted between the concentration of tear film SP and TNS in T1D (r = -0.49; P < 0.001) and corneal nerve fibre density (r = 0.45; P < 0.001). The concentration of tear film CGRP was correlated significantly with the reduction of corneal nerve fibre density (r = 0.41; P = 0.01) in T1D.
Tear film SP may provide a potential non-invasive biomarker for assessing neuropathy in T1D.
探讨角膜去神经支配后，神经肽 P 物质（SP）和降钙素基因相关肽（CGRP）在泪液中的浓度变化及其与糖尿病周围神经病变（DPN）的关系。
63 例 1 型糖尿病/2 型糖尿病（T1D/T2D）患者和 34 名年龄匹配的健康对照者接受了详细的神经病变评估，包括总神经病变评分（TNS）。酶联免疫吸附试验（ELISA）测定泪液中 SP 和 CGRP 的浓度。使用角膜共聚焦显微镜对角膜基底部神经丛进行成像。定量测量角膜神经纤维长度、纤维密度、分支密度、总分支密度、神经分形维数和下涡长度。
在 T1D 中，DPN 患者（130 [61-692]pg/mL）泪液中 SP 浓度中位数[IQR]明显低于对照组（763 [405-1555]pg/mL，P<0.01）和无 DPN 患者（914 [339-1832]pg/mL，P=0.01）；CGRP 浓度无变化。在 T2D 中，无论是否存在神经病变，糖尿病患者与对照组之间神经肽均无差异。在 T1D 和 T2D 中，DPN 患者和无 DPN 患者与对照组之间角膜神经参数存在显著差异。在 T1D 中，泪膜 SP 浓度与 TNS 之间存在显著相关性（r=-0.49；P<0.001）和角膜神经纤维密度（r=0.45；P<0.001）。在 T1D 中，泪膜 CGRP 浓度与角膜神经纤维密度降低显著相关（r=0.41；P=0.01）。
泪膜 SP 可能为评估 T1D 神经病变提供一种潜在的非侵入性生物标志物。
