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Dose-Dependent Effect of Mouse Nerve Growth Factor Eye Drops on Corneal Nerve Regeneration in Rabbits after LASIK |
Lu Jiang1, 2, Ye Yu1 , Meng Lin1 , Qianwen Gong1 , Zhiqiang Xu1 , Liang Hu1 |
1 Eye Hospital of Wenzhou Medical University, Wenzhou 325027, China 2 Hankou Aier Eye Hospital, Wuhan 430000, China |
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Abstract Objective: To investigate the effect of different concentrations of mouse nerve growth factor (mNGF) in eye drops on rabbits' central corneal nerve regeneration after laser in situ keratomileusis. Methods: In this experimental study, 39 New Zealand white rabbits were included and randomly assigned to 5 groups: normal saline group (normal saline, 7 rabbits, 14 eyes), hycosan group (0.1% hycosan, 8 rabbits, 16 eyes), NGF50 group (50 µg/mL, 8 rabbits, 16 eyes), NGF100 group (100 µg/mL, 8 rabbits, 16 eyes) and NGF200 group (200 µg/mL, 8 rabbits, 16 eyes). Central corneal subbasal nerve densities (SNDs) and superficial stroma nerve densities (SSNDs) were measured by confocal microscopy Ⅲ and were compared before surgery, 1 week, 1 month, 2 months and 3 months after surgery. Repeated measures and one-way analysis of variance were used for comparing the differences between different time points for these groups. Results: The differences in preoperative SNDs and SSNDs in the normal saline group, hycosan group, NGF50 group, NGF100 group and NGF200 group were not statistically significant (F=1.371, P=0.252; F=0.372, P=0.828). Compared with preoperative values, all nerve parameters of the 5 groups decreased at 1 week (all P<0.05) postoperatively, but the differences among the 5 groups were not statistically significant (F=1.905, P=0.119; F=0.923, P=0.455). SNDs in the NGF100 group and NGF200 group were significantly higher than in the other 3 groups at 1 month after surgery (all P<0.05); SNDs in the NGF200 group were significantly higher than in the other groups at 2 months and 3 months postoperatively (all P<0.05). SSNDs in the NGF200 group were significantly higher than in the other groups at 1 and 2 months after surgery (all P<0.05). At 3 months after surgery, SSNDs in the NGF200 group were significantly higher than those in the NGF50 group and the 2 nonNGF groups (all P<0.05). The NGF50 group and NGF100 group had higher densities than the 2 non-NGF groups (all P<0.05). Conclusions: mNGF eye drops have a significant effect on promoting corneal nerve repair in different periods following LASIK, and the effect is highest in the NGF200 group.
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Received: 18 October 2019
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Fund: Wenzhou Science and Technology Plan Project (Y20160442); Natural Science Foundation of Zhejiang Province (LY17H120005) |
Corresponding Authors:
Liang Hu, Eye Hospital of Wenzhou Medical University, Wenzhou 325027, China (Email: liang_hu@live.cn)
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[1] |
Liu M, Chen Y, Wang D, et al. Clinical outcomes after smile and femtosecond laser-assisted lasik for myopia and myopic astigmatism: A prospective randomized comparative study. Cornea, 2016, 35(2): 210-216. DOI: 10.1097/ ICO.0000000000000707.
|
[2] |
Moshirfar M, Jehangir N, Fenzl CR, et al. LASIK enhancement: Clinical and surgical management. J Refract Surg, 2017, 33(2): 116-127. DOI: 10.3928/1081597X-20161202-01.
|
[3] |
Shen Z, Zhu Y, Song X, et al. Dry eye after small incision lenticule extraction (SMILE) versus femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia: A meta-analysis. PLoS One, 2016, 11(12): e0168081. DOI: 10.1371/journal. pone.0168081.
|
[4] |
胡启迪, 许玲俐, 马蓉, 等. FS-LASIK与去瓣LASEK术后干 眼比较. 中华眼视光学与视觉科学杂志, 2019, 21(6): 408-413. DOI: 10.3760/cma.j.issn.1674-845X.2019.06.002.
|
[5] |
Mai EL, Lian IB, Chang DC. Assessment of contrast sensitivity loss after intrastromal femtosecond laser and LASIK procedure. Int J Ophthalmol 2016, 9(12): 1798-1801. DOI: 10.18240/ ijo.2016.12.16.
|
[6] |
郭丰芳,方学军. FS-LASIK与SMILE术后干眼参数与角膜知 觉的比较. 中华眼视光学与视觉科学杂志, 2019, 21(12): 930- 936. DOI: 10.3760/cma.j.issn.1674-845X.2019.12.009.
|
[7] |
Wang B, Naidu RK, Chu R, et al. Dry eye disease following refractive surgery: a 12-month follow-up of SMILE versus FSLASIK in high myopia. J Ophthalmol, 2015, 2015: 132417. DOI: 10.1155/2015/132417.
|
[8] |
Shtein RM. Post-LASIK dry eye. Expert Rev Ophthalmol, 2011, 6(5): 575-582. DOI: 10.1586/eop.11.56.
|
[9] |
Benson N, Matsuura T, Smirnov S, et al. Systems pharmacology of the nerve growth factor pathway: use of a systems biology model for the identification of key drug targets using sensitivity analysis and the integration of physiology and pharmacology. Interface Focus, 2013, 3(2): 20120071. DOI: 10.1098/ rsfs.2012.0071.
|
[10] |
Sone Y, Takatori S, Ochi E, et al. Nerve growth factor facilitates the innervation of perivascular nerves in tumor-derived neovasculature in the mouse cornea. Pharmacology, 2017, 99(1- 2): 57-66. DOI: 10.1159/000450582.
|
[11] |
Park JH, Kang SS, Kim JY, et al. Nerve growth factor attenuates apoptosis and inflammation in the diabetic cornea. Invest Ophthalmol Vis Sci, 2016, 57(15): 6767-6775. DOI: 10.1167/ iovs.16-19747.
|
[12] |
Wu Y, Chu R, Zhou X, et al. Determination of the nerve growth factor level in the central cornea after LASIK and Epi-LASIK treatment in a rabbit model system. Cornea, 2009, 28(10): 1144- 1148. DOI: 10.1097/ICO.0b013e3181a2a7e3.
|
[13] |
Lambiase A, Coassin M, Sposato V, et al. NGF topical application in patients with corneal ulcer does not generate circulating NGF antibodies. Pharmacol Res, 2007, 56(1): 65-69. DOI: 10.1016/j.phrs.2007.03.007.
|
[14] |
Coassin M, Lambiase A, Costa N, et al. Efficacy of topical nerve growth factor treatment in dogs affected by dry eye. Graefes Arch Clin Exp Ophthalmol, 2005, 243(2): 151-155. DOI: 10.1007/s00417-004-0955-2.
|
[15] |
Cellini M, Bendo E, Bravetti GO, et al. The use of nerve growth factor in surgical wound healing of the cornea. Ophthalmic Res, 2006, 38(4): 177-181. DOI: 10.1159/000092626.
|
[16] |
Patel DV, McGhee CN. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: A review. Br J Ophthalmol, 2009, 93(7): 853-860. DOI: 10.1136/bjo.2008.150615.
|
[17] |
朱丹丹, 陈辉. 神经生长因子滴眼液对LASIK术后角膜瓣神 经修复的影响. 眼科研究, 2009, 27(5): 420-424. DOI: 10.3760/ cma.j.issn.2095-0160.2009.05.014.
|
[18] |
Ma K, Yan N, Huang Y, et al. Effects of nerve growth factor on nerve regeneration after corneal nerve damage. Int J Clin Exp Med, 2014, 7(11): 4584-4589.
|
[19] |
Joo MJ, Yuhan KR, Hyon JY, et al. The effect of nerve growthfactor on corneal sensitivity after laser in situ keratomileusis. Arch Ophthalmol, 2004, 122(9): 1338-1341. DOI: 10.1001/ archopht.122.9.1338.
|
[20] |
Ferrari MP, Mantelli F, Sacchetti M, et al. Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial. BioDrugs, 2014, 28(3): 275-283. DOI: 10.1007/ s40259-013-0079-5.
|
[21] |
Cruzat A, Qazi Y, Hamrah P. In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf, 2017, 15(1): 15- 47. DOI: 10.1016/j.jtos.2016.09.004.
|
[22] |
张栋, 胡亮, 陈佳, 等. 应用共聚焦显微镜观察干眼病及 配戴角膜接触镜对角膜上皮下神经密度影响 . 中国实 用眼科杂志, 2013, 31(6): 704-708. DOI: 10.3760/cma. j.issn.1006-4443.2013.06.014.
|
[23] |
Li B, Sheng X, Bao L, et al. Seasonal changes in expression of nerve growth factor and its receptors TrkA and p75 in the ovary of wild ground squirrel (Citellus dauricus Brandt). J Ovarian Res, 2014, 7: 3. DOI: 10.1186/1757-2215-7-3.
|
[24] |
Blanco-Mezquita T, Martinez-Garcia C, Proença R, et al. Nerve growth factor promotes corneal epithelial migration by enhancing expression of matrix metalloprotease-9. Invest Ophthalmol Vis Sci, 2013, 54(6): 3880-3890. DOI: 10.1167/ iovs.12-10816.
|
[25] |
Manni L, Rocco ML, Bianchi P, et al. Nerve growth factor: basic studies and possible therapeutic applications. Growth Factors, 2013, 31(4): 115-122. DOI: 10.3109/08977194.2013.804073.
|
[26] |
Nucci C, Strouthidis NG, Khaw PT. Neuroprotection and other novel therapies for glaucoma. Curr Opin Pharmacol, 2013, 13(1): 1-4. DOI: 10.1016/j.coph.2012.10.009.
|
[27] |
Shaheen BS, Bakir M, Jain S. Corneal nerves in health and disease. Surv Ophthalmol, 2014, 59(3): 263-285. DOI: 10.1016/ j.survophthal.2013.09.002.
|
[28] |
Chao C, Golebiowski B, Zhao X, et al. Long-term effects of LASIK on corneal innervation and tear neuropeptides and the associations with dry eye. J Refract Surg, 2016, 32(8): 518-524. DOI: 10.3928/1081597X-20160603-01.
|
[29] |
Levitt AE, Galor A, Weiss JS, et al. Chronic dry eye symptoms after LASIK: parallels and lessons to be learned from other persistent post-operative pain disorders. Mol Pain, 2015, 11: 21. DOI: 10.1186/s12990-015-0020-7.
|
[30] |
Rosenfeld SI. Evaluation and management of post-LASIK dry eye syndrome. Int Ophthalmol Clin, 2010, 50(3): 191-199. DOI: 10.1097/IIO.0b013e3181e2469b.
|
[31] |
Kobashi H, Kamiya K, Shimizu K. Dry eye after small incision lenticule extraction and femtosecond laser-assisted LASIK: Meta-analysis. Cornea, 2017, 36(1): 85-91. DOI: 10.1097/ ICO.0000000000000999.
|
[32] |
Lee HK, Lee KS, Kim HC, et al. Nerve growth factor concentration and implications in photorefractive keratectomy vs laser in situ keratomileusis. Am J Ophthalmol, 2005, 139(6): 965-971. DOI: 10.1016/j.ajo.2004.12.051.
|
[33] |
Klenkler B, Sheardown H, Jones L. Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology. Ocul Surf, 2007, 5(3): 228-239. DOI: 10.1016/s1542- 0124(12)70613-4.
|
[34] |
Lisi S, Sisto M, Ribatti D, et al. Chronic inflammation enhances NGF-β/TrkA system expression via EGFR/MEK/ERK pathway activation in Sjögren's syndrome. J Mol Med (Berl), 2014, 92(5): 523-537. DOI: 10.1007/s00109-014-1130-9.
|
[35] |
刘畅, 张一川, 乔诗凝, 等. LASIK与LASEK术后兔角膜神经 损伤和修复的实验研究.眼科, 2011, 20(6): 391-396.
|
[36] |
丁冬梅, 陈辉, 桑爱民, 等. 神经生长因子滴眼液对兔眼准 分子激光原位角膜磨镶术后角膜神经修复的影响.眼视光 学杂志, 2008, 10(2): 115-118. DOI: 10.3760/cma.j.issn.1674- 845X.2008.02.009.
|
[37] |
张莎莎, 桂四凤, 钱倩, 等. 神经生长因子滴眼液对兔眼 LASIK术后角膜神经修复的影响. 中华眼视光学与视觉科 学杂志, 2017, 19(1): 33-39. DOI: 10.3760/cma.j.issn.1674- 845X.2017.01.007.
|
|
|
|