Abstract：
The dense nerve and thin vascular structure of the corneal tissue provide the refractive function in healthy eyes. Diabetes mellitus causes ocular complications including corneal opacification because of corneal nerve degeneration. Diabetic neurotrophic keratopathy is characterized by reduced corneal sensitivity, delayed corneal wound healing, and nerve degeneration. Neurotization and vascularization inhibit each other in the cornea. Macrophages contribute to the corneal neovascularization. To investigate the role of macrophage in neurotrophic keratopathy, clodronate liposome was subconjunctivally injected into diabetic db/db mice with neurotrophic keratopathy. The clodronate liposome treatment decreased F4/80+ macrophage infiltration into the corneal epithelium, and improved corneal nerve involvement in diabetic db/db mice. Furthermore, we found that interleukin (IL)-1β and IL-34 mRNA expression was increased in the corneal epithelium of clodronate-treated diabetic db/db mice. These cytokines contribute to the maintenance of nerve tissues via microglia and nerve regeneration; however, their role in corneal nerve involvement remains unknown. Notably, the intraocular injection of recombinant IL-1β and IL-34 promoted nerve regeneration in the cornea of diabetic db/db mice. These results suggest that clodronate liposome treatment contributes to nerve regeneration during corneal involvement via IL-1β and IL-34 signaling.
摘要：
角膜组织的致密神经和薄血管结构提供了健康眼睛的屈光功能。由于角膜神经变性，糖尿病会引起眼部并发症，包括角膜混浊。糖尿病性神经营养性角膜病变的特征是角膜敏感性降低，角膜伤口延迟愈合，和神经退化。神经化和血管形成在角膜中相互抑制。巨噬细胞有助于角膜新生血管形成。探讨巨噬细胞在神经营养性角膜病变中的作用,将氯膦酸盐脂质体结膜下注射到患有神经营养性角膜病变的糖尿病db/db小鼠中。氯膦酸盐脂质体治疗减少了F4/80+巨噬细胞向角膜上皮的浸润，改善糖尿病db/db小鼠的角膜神经受累。此外，我们发现，白细胞介素（IL）-1β和IL-34mRNA表达在clodrate治疗的糖尿病db/db小鼠的角膜上皮中增加。这些细胞因子有助于通过小胶质细胞和神经再生维持神经组织;然而,它们在角膜神经受累中的作用尚不清楚.值得注意的是,眼内注射重组IL-1β和IL-34促进糖尿病db/db小鼠角膜神经再生。这些结果表明，氯膦酸盐脂质体治疗有助于通过IL-1β和IL-34信号传导参与角膜过程中的神经再生。
