NGF and CNTF expression and regulation mechanism by miRNA in acute paralytic strabismus

  • Hua Liu
  • Nian Tan
  • Duo XuEmail author
  • Chong-Yi Li
  • Guang-Jun Xian
Original Paper



Nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) are well-known neurotrophic factors and widely used in the clinical treatment for its promotion effect on peripheral nerve regeneration. And they were also recommended for the acute paralytic strabismus treatment. However, whether the NGF and CNTF have protective effect for the extraocular muscles of acute paralytic strabismus patients is still poorly understood.


In this study, we want to evaluate the biological function of NGF and CNTF on the extraocular muscle cells and reveale the regulation mechanism behind it.


Firstly, the relative expression of ngf and cntf was assessed by quantitative real-time RT-PCR. Then, the influence of NGF and CNTF on the extraocular muscle cell proliferation was determined by CCK-8. The inflammatory response in muscle cells after NGF and CNTF treatment was evaluated by ELISA and ROS detection. In addition to this, the up-stream regulation of the ngf and cntf expression was also studied. The TargetScan was used for the predication of potential miRNAs targeting with ngf and cntf 30-UTR, which is soon confirmed by luciferase activity assay. Results: all the results in this research indicated that NGF and CNTF could promote the muscle cell proliferation and inhibit the inflammatory levels, then exert protective effect on the muscle cell function.


All the results in this research indicated that NGF and CNTF could promote the muscle cell proliferation and inhibit the inflammatory levels, then exert protective effect on the muscle cell function.


It was conceivable that let 7-5p was the up-stream regulator of ngf and cntf, and let 7-5p might serve as a potential molecular target for acute paralytic strabismus treatment.


Acute paralytic strabismus miRNAs Let 7-5p NGF CNTF 



The research did not receive any specific funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest regarding the publication of this paper.


  1. 1.
    Clark RA (2015) The role of extraocular muscle pulleys in incomitant non-paralytic strabismus. Middle East Afr J Ophthalmol 22(3):279–285CrossRefGoogle Scholar
  2. 2.
    Jeon H, Jung JH, Yoon JA, Choi H (2019) Strabismus is correlated with gross motor function in children with spastic cerebral palsy. Curr Eye Res 44(11):1258–1263CrossRefGoogle Scholar
  3. 3.
    Schiavi C (2000) Paralytic strabismus. Curr Opin Ophthalmol 11:318–323CrossRefGoogle Scholar
  4. 4.
    Flanders M (2014) Restrictive strabismus: diagnosis and management. Am Orthopt J 64(1):54–63CrossRefGoogle Scholar
  5. 5.
    Kim H, Li Q, Hempstead BL, Madri JA (2004) Paracrine and autocrine functions of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in brain-derived endothelial cells. J Biol Chem 279:33538–33546CrossRefGoogle Scholar
  6. 6.
    Rocco ML, Soligo M, Manni L, Aloe L (2018) Nerve growth factor: early studies and recent clinical trials. Curr Neuropharmacol 16(10):1455–1465CrossRefGoogle Scholar
  7. 7.
    Cui J, Zhou B, Ross SA, Zempleni J (2017) Nutrition, microRNAs, and human health. Adv Nutr 8(1):105–112CrossRefGoogle Scholar
  8. 8.
    Zendjabil M, Favard S, Tse C, Abbou O, Hainque B (2017) The microRNAs as biomarkers: what prospects? C R Biol 340(2):114–131CrossRefGoogle Scholar
  9. 9.
    Gu Q (1995) Involvement of nerve growth factor in visual cortex plasticity. Rev Neurosci 6(4):329–351CrossRefGoogle Scholar
  10. 10.
    Khan-Malek R, Wang Y (2017) Statistical analysis of quantitative RT-PCR results. Methods Mol Biol 1641:281–296CrossRefGoogle Scholar
  11. 11.
    Gong W, Qie S, Huang P, Xi J (2018) Protective effect of miR-374a on chemical hypoxia-induced damage of PC12 cells in vitro via the GADD45α/JNK signaling pathway. Neurochem Res 43(3):581–590CrossRefGoogle Scholar
  12. 12.
    Xia Q, Zheng Y, Jiang W, Huang Z, Wang M, Rodriguez R, Jin X (2016) Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells. Oncol Lett 12(3):1826–1832CrossRefGoogle Scholar
  13. 13.
    Holen I, Lefley DV, Francis SE, Rennicks S, Bradbury S, Coleman RE, Ottewell P (2016) IL-1 drives breast cancer growth and bone metastasis in vivo. Oncotarget 7(46):75571–75584CrossRefGoogle Scholar
  14. 14.
    Xu J, Lü XW, Huang Y, Zhu PL, Li J (2009) Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. J Pharm Pharmacol 61:503–510CrossRefGoogle Scholar
  15. 15.
    Taggart CC, Cryan SA, Weldon S, Gibbons A, Greene CM, Kelly E, Low TB, O’neill SJ, McElvaney NG (2005) Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding. J Exp Med 202(12):1659–1668CrossRefGoogle Scholar
  16. 16.
    Kim B (2017) Western blot techniques. Methods Mol Biol 1606:133–139CrossRefGoogle Scholar
  17. 17.
    Wang Y, Li M, Dong C, Ma Y, Xiao L, Zuo S, Gong Y, Ren T, Sun B (2019) Linc00152 knockdown inactivates the Akt/mTOR and Notch1 pathways to exert its anti-hemangioma effect. Life Sci 223:22–28CrossRefGoogle Scholar
  18. 18.
    Christiansen SP, Baker RS, Madhat M, Porter JD (1994) Lengthening extraocular muscle with autologous muscle transplants. Strabismus 2(1):29–39CrossRefGoogle Scholar
  19. 19.
    Chen J, Chu YF, Chen JM, Li BC (2010) Synergistic effects of NGF, CNTF and GDNF on functional recovery following sciatic nerve injury in rats. Adv Med Sci 55(1):32–42CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2020

Authors and Affiliations

  • Hua Liu
    • 1
  • Nian Tan
    • 1
  • Duo Xu
    • 1
    Email author
  • Chong-Yi Li
    • 1
  • Guang-Jun Xian
    • 1
  1. 1.Department of Ophthalmology, Daping HospitalArmy Medical Center of PLAChongqingChina

Personalised recommendations