Cortina M Soledad, He Jiucheng, Li Na, Bazan Nicolas G, Bazan Haydee E P
Department of Ophthalmology, University of Illinois Medical Center, Chicago, USA.
Arch Ophthalmol. 2012 Jan;130(1):76-83. doi: 10.1001/archophthalmol.2011.287. Epub 2011 Sep 12.
To assess function of regenerated corneal nerves in correlation with epithelial wound healing after experimental nerve damage in rabbits treated with pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA).
An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with βIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation.
Eight weeks after surgery, calcitonin gene-related peptide-positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial-derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area.
Pigment epithelial-derived factor plus DHA promotes regeneration of calcitonin gene-related peptide-positive corneal nerves, accelerating wound healing and return of corneal sensitivity.
Pigment epithelial-derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.
评估在接受色素上皮衍生因子（PEDF）加二十二碳六烯酸（DHA）治疗的兔实验性神经损伤后，再生角膜神经功能与上皮伤口愈合的相关性。
对成年新西兰兔的右眼进行8毫米的基质剥离。用PEDF+DHA治疗6周。每周用科谢-博内角膜知觉计测量角膜感觉。8周后，用βIII-微管蛋白、降钙素基因相关肽和P物质抗体进行免疫荧光检测以量化神经。此外，在板层角膜切除术后用PEDF+DHA治疗兔4周，随后进行8毫米的上皮清创术并评估上皮缺损情况。手术后1周，用抗Ki67抗体对角膜进行染色以评估细胞增殖。
手术后8周，PEDF+DHA组中降钙素基因相关肽阳性神经纤维与正常兔角膜相似，但在赋形剂组中减少。P物质定位于上皮下丛，但无论治疗如何，在神经损伤后均出现在上皮细胞中。手术后5周，PEDF+DHA组角膜敏感性增加，并在8周时达到正常值。色素上皮衍生因子加DHA可促进板层角膜切除术后上皮伤口愈合。上皮损伤后1周，角膜缘区域Ki67阳性细胞增加。
色素上皮衍生因子加DHA促进降钙素基因相关肽阳性角膜神经的再生，加速伤口愈合和角膜敏感性恢复。
色素上皮衍生因子加DHA代表了一种神经再生的新方法，是预防手术后或眼表疾病后严重干眼的潜在治疗方法。
