He Jiucheng, Pham Thang Luong, Kakazu Azucena, Bazan Haydee E P
Neuroscience Center of Excellence and Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center New Orleans, New Orleans, LA.
Neuroscience Center of Excellence and Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center New Orleans, New Orleans, LA
Diabetes. 2017 Sep;66(9):2511-2520. doi: 10.2337/db17-0249. Epub 2017 Jun 7.
Diabetic keratopathy decreases corneal sensation and tear secretion and delays wound healing after injury. In the current study, we tested the effect of treatment with pigment epithelium-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a mouse model of diabetes with or without corneal injury. The study was performed in streptozotocin-induced diabetic mice (C57BL/6). Ten weeks after streptozotocin injection, diabetic mice showed significant decreases of corneal sensitivity, tear production, and epithelial subbasal nerve density when compared with age-matched normal mice. After diabetic mice were wounded in the right eye and treated in both eyes with PEDF+DHA for 2 weeks, there was a significant increase in corneal epithelial nerve regeneration and substance P-positive nerve density in both wounded and unwounded eyes compared with vehicle-treated corneas. There also was elevated corneal sensitivity and tear production in the treated corneas compared with vehicle. In addition, PEDF+DHA accelerated corneal wound healing, selectively recruited type 2 macrophages, and prevented neutrophil infiltration in diabetic wounded corneas. These results suggest that topical treatment with PEDF+DHA promotes corneal nerve regeneration and wound healing in diabetic mice and could potentially be exploited as a therapeutic option for the treatment of diabetic keratopathy.
糖尿病性角膜病变会降低角膜感觉和泪液分泌，并延迟损伤后的伤口愈合。在本研究中，我们在有或没有角膜损伤的糖尿病小鼠模型中测试了色素上皮衍生因子（PEDF）与二十二碳六烯酸（DHA）联合治疗对角膜神经再生的影响。该研究在链脲佐菌素诱导的糖尿病小鼠（C57BL/6）中进行。链脲佐菌素注射10周后，与年龄匹配的正常小鼠相比，糖尿病小鼠的角膜敏感性、泪液分泌和上皮基底膜下神经密度显著降低。糖尿病小鼠右眼受伤后，双眼用PEDF+DHA治疗2周，与用赋形剂处理的角膜相比，受伤和未受伤眼睛的角膜上皮神经再生和P物质阳性神经密度均显著增加。与赋形剂相比，治疗后的角膜角膜敏感性和泪液分泌也有所提高。此外，PEDF+DHA加速了角膜伤口愈合，选择性地募集了2型巨噬细胞，并防止了糖尿病受伤角膜中的中性粒细胞浸润。这些结果表明，局部应用PEDF+DHA可促进糖尿病小鼠的角膜神经再生和伤口愈合，并有可能作为治疗糖尿病性角膜病变的一种治疗选择。
