Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration
Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration
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角膜上皮源性神经营养因子促进神经再生
DOI：
10.1167/iovs.16-21372
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发表时间：
2017-09-01
影响因子：
4.4
通讯作者：
Zhou, Qingjun
中科院分区：
文献类型：
--
作者：
Di, Guohu;Qi, Xia;Zhou, Qingjun
目的。探讨角膜上皮中神经营养因子的表达，并评价其对小鼠三叉神经节（TG）神经突生长和角膜神经再生的影响。比较完整、再生和再生小鼠角膜上皮中神经营养因子的表达。用小鼠角膜上皮细胞条件培养基处理小鼠原代TG神经元。采用神经生长因子（NGF）中和抗体和神经胶质细胞源性神经营养因子（GDNF）中和抗体评价其在小鼠角膜神经再生和TG神经突生长中的作用。进一步观察NGF和GDNF对糖尿病小鼠角膜神经再生的促进作用。在角膜上皮再生过程中，NGF和GDNF表达显著上调，并恢复到损伤前水平，这与角膜基底下神经再生的进展一致。角膜上皮细胞条件培养基促进TG神经突的生长，分支延长，伸长。此外，阻断NGF或GDNF均可显著损害条件培养基对正常小鼠角膜神经突生长的促进作用或角膜神经再生。此外，与正常小鼠相比，糖尿病再生角膜上皮中NGF和GDNF的表达减弱，而外源性NGF或GDNF的补充促进了糖尿病小鼠角膜上皮和神经的再生。角膜上皮表达多种神经营养因子，其中NGF和GDNF可能在角膜神经再生中发挥重要作用。
PURPOSE. To explore the neurotrophic factor expression in corneal epithelium and evaluate their effects on the trigeminal ganglion (TG) neurite outgrowth and corneal nerve regeneration in mice.METHODS. The expression of neurotrophic factors was compared among the intact, regenerating, and regenerated mouse corneal epithelium. Mouse primary TG neurons were treated with the conditioned medium of mouse corneal epithelial cells. Nerve growth factor (NGF) neutralizing antibody and glial cell-derived neurotrophic factor (GDNF) neutralizing antibody were used to evaluate their roles in mouse corneal nerve regeneration and TG neurite outgrowth. The promoting effects of NGF and GDNF for the corneal nerve regeneration were further evaluated in the diabetic mice.RESULTS. The expression of NGF and GDNF showed significant up-regulation in regenerating corneal epithelium and return to the preinjury levels in the regenerated epithelium, which was consistent with the progress of corneal subbasal nerve regeneration. The conditioned medium of corneal epithelial cells promoted the TG neurite outgrowth with extended branching and elongation. Furthermore, the blockage of either NGF or GDNF significantly impaired the promotion of the neurite outgrowth by the conditioned medium or the corneal nerve regeneration in normal mice. Moreover, the expression of NGF and GDNF was attenuated in the diabetic regenerating corneal epithelium as compared to that in normal mice, while exogenous NGF or GDNF supplement promoted the corneal epithelial and nerve regeneration in diabetic mice.CONCLUSIONS. Corneal epithelium expresses multiple neurotrophic factors, among which NGF and GDNF may play an important role in the corneal nerve regeneration.