Trans-lamina Cribrosa Pressure Difference Activates Mechanical Stress Signal Transduction to Induce Glaucomatous Optic Neuropathy: A Hypothesis

  • Jingxue Zhang
  • Shen Wu
  • Ningli WangEmail author
Part of the Advances in Visual Science and Eye Diseases book series (AVSED, volume 1)


Glaucoma is the leading cause of irreversible blindness in the world. According to a recent meta-analysis, the global prevalence of glaucoma has reached 3.54%, and the number of people with glaucoma worldwide would increase to 110 million in 2040. Glaucoma, as one of the most common eye conditions resulting in blindness, has been recognized as a major public health challenge [1].


  1. 1.
    Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–90.CrossRefGoogle Scholar
  2. 2.
    De Moraes CG, Demirel S, Gardiner SK, et al. Effect of treatment on the rate of visual field change in the ocular hypertension treatment study observation group. Investig Ophthalmol Vis Sci. 2012;53(4):1704–9.CrossRefGoogle Scholar
  3. 3.
    Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7.CrossRefGoogle Scholar
  4. 4.
    Fechtner RD, Weinreb RN. Mechanisms of optic nerve damage in primary open angle glaucoma. Surv Ophthalmol. 1994;39(1):23–42.CrossRefGoogle Scholar
  5. 5.
    Burgoyne CF, Downs JC. Premise and prediction-how optic nerve head biomechanics underlies the susceptibility and clinical behavior of the aged optic nerve head. J Glaucoma. 2008;17(4):318–28.CrossRefGoogle Scholar
  6. 6.
    Yamamoto T, Kitazawa Y. Vascular pathogenesis of normal-tension glaucoma: a possible pathogenetic factor, other than intraocular pressure, of glaucomatous optic neuropathy. Prog Retin Eye Res. 1998;17(1):127–43.CrossRefGoogle Scholar
  7. 7.
    Liang YB, Friedman DS, Zhou Q, et al. Prevalence of primary open angle glaucoma in a rural adult Chinese population: the Handan eye study. Investig Ophthalmol Visual Sci. 2011;52(11):8250–7.CrossRefGoogle Scholar
  8. 8.
    Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117(2):259–26.CrossRefGoogle Scholar
  9. 9.
    Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5):763–8.CrossRefGoogle Scholar
  10. 10.
    Berdahl JP, Fautsch MP, Stinnett SS, et al. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci. 2008;49(12):5412–8.CrossRefGoogle Scholar
  11. 11.
    Wostyn P, De Groot V, Van Dam D, et al. Fast circulation of cerebrospinal fluid: an alternative perspective on the protective role of high intracranial pressure in ocular hypertension. Clin Exp Optom. 2016;99(3):213–8.CrossRefGoogle Scholar
  12. 12.
    Ren R, Zhang X, Wang N, et al. Cerebrospinal fluid pressure in ocular hypertension. Acta Ophthalmol. 2011;89(2):e142–8.CrossRefGoogle Scholar
  13. 13.
    Siaudvytyte L, Januleviciene I, Daveckaite A, et al. Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma. Eye. 2015;29(10):1242–50.CrossRefGoogle Scholar
  14. 14.
    Yang D, Fu J, Hou R, et al. Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys. Invest Ophthalmol Vis Sci. 2014;55(5):3067–73.CrossRefGoogle Scholar
  15. 15.
    Zhang Z, Wu S, Jonas JB, et al. Dynein, kinesin and morphological changes in optic nerve axons in a rat model with cerebrospinal fluid pressure reduction: the Beijing Intracranial and Intraocular Pressure (iCOP) study. Acta Ophthalmol. 2016;94(3):266–75.CrossRefGoogle Scholar
  16. 16.
    Hernandez MR, Igoe F, Neufeld AH. Extracellular matrix of the human optic nerve head. Am J Ophthalmol. 1986;102(2):139–48.CrossRefGoogle Scholar
  17. 17.
    Morrison JC, Jerdan JA, L’Hernault NL, et al. The extracellular matrix composition of the monkey optic nerve head. Invest Ophthalmol Vis Sci. 1988;29(7):1141–50.Google Scholar
  18. 18.
    Hernandez MR, Igoe F, Neufeld AH. Cell culture of the human lamina cribrosa. Invest Ophthalmol Vis Sci. 1988;29(1):78–89.PubMedGoogle Scholar
  19. 19.
    Ingber DE. Tensegrity: the architectural basis of cellular mechano-transduction[J]. Annu Rev Physiol. 2003;59(1):575–99.CrossRefGoogle Scholar
  20. 20.
    Visavadiya NP, Keasey MP, Razskazovskiy V, et al. Integrin-FAK signaling rapidly and potently promotes mitochondrial function through STAT3. Cell Commun Signal. 2016;14(1):32.CrossRefGoogle Scholar
  21. 21.
    Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science. 1995;268(5208):233–9.CrossRefGoogle Scholar
  22. 22.
    Cabodi S, Di Stefano P, Leal Mdel P, et al. Integrins and signal transduction. Adv Exp Med Biol. 2010;674:43–54.CrossRefGoogle Scholar
  23. 23.
    Martins RP, Finan JD, Guilak F, et al. Mechanical regulation of nuclear structure and function. Annu Rev Biomed Eng. 2012;14:431–55.CrossRefGoogle Scholar
  24. 24.
    Tajik A, Zhang Y, Wei F, et al. Transcription upregulation via force-induced direct stretching of chromatin. Nat Mater. Dec 2016;15(12):1287–96.CrossRefGoogle Scholar
  25. 25.
    George CH, Higgs GV, Lai FA. Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ Res. 2003;93(6):531–40.CrossRefGoogle Scholar
  26. 26.
    Liu B, Lu S, Zheng S, et al. Two distinct phases of calcium signalling under flow. Cardiovasc Res. 2011;91(1):124–33.CrossRefGoogle Scholar
  27. 27.
    Bhosale G, Sharpe JA, Sundier SY, et al. Calcium signaling as a mediator of cell energy demand and a trigger to cell death. Ann N Y Acad Sci. 2015;1350:107–16.CrossRefGoogle Scholar
  28. 28.
    Zou H, Lifshitz LM, Tuft RA, et al. Visualization of Ca2+ entry through single stretch-activated cation channels. Proc Natl Acad Sci USA. 2002;99(9):6404–9.CrossRefGoogle Scholar
  29. 29.
    Tehrani S, Davis L, Cepurna WO, et al. Astrocyte structural and molecular response to elevated intraocular pressure occurs rapidly and precedes axonal tubulin rearrangement within the optic nerve head in a rat model. PLoS One. 2016;11(11):e0167364.CrossRefGoogle Scholar
  30. 30.
    Santos AR, Corredor RG, Obeso BA, et al. beta1 integrin-focal adhesion kinase (FAK) signaling modulates retinal ganglion cell (RGC) survival. PLoS One. 2012;7(10):e48332.CrossRefGoogle Scholar
  31. 31.
    Ryskamp DA, Witkovsky P, Barabas P, et al. The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells. J Neurosci. 2011;31(19):7089–101.CrossRefGoogle Scholar
  32. 32.
    Krizaj D, Ryskamp DA, Tian N, et al. From mechanosensitivity to inflammatory responses: new players in the pathology of glaucoma. Curr Eye Res. 2014;39(2):105–19.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
  2. 2.Beijing Ophthalmology & Visual Sciences Key LaboratoryBeijingChina

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