The Glaucoma Book pp 1011-1014 | Cite as

What Really Causes Glaucoma?

  • John R. Samples


Glaucoma can be defined in many different ways, as evidenced in this text. The most common definition is based on anatomy and pressure, with open angle glaucoma being most common among Caucasians in North America, low or normal tension glaucoma being most common among the Japanese, and angle closure being most common among other Asians. (Such clear delineations are not currently recognized in other ethnic groups.) Certain regions of the world give rise to the special circumstances of exfoliation. In the U.S., I am continually surprised with the discovery of new geographic foci of exfoliation. Regionally, it has been recognized for decades that exfoliation has a higher than normal prevalence in the greater Minneapolis area and around Minnesota - it is likely that this is due to the large number of individuals of Scandinavian descent. A week before writing this, I found out that exfoliation was also very common in the Salt Lake City area, where again northern European heritage is considered the causal factor. The genetics of exfoliation may eventually be studied more extensively in the geographic areas that are most highly affected. Ultimately, what really causes glaucoma is likely to be defined in genetic terms, just as exfoliation (but not necessarily exfoliative glaucoma) has been. Risk factors and “environmental factors,” as enumerated in the first chapters of this text, will always be important and have an impact upon the susceptible eye.


Intraocular Pressure Open Angle Glaucoma Trabecular Meshwork Angle Closure Normal Tension Glaucoma 


  1. 1.
    Alvarado J, Murohy C, Polansky J, Juster R. Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci. 1981;21:714–727.PubMedGoogle Scholar
  2. 2.
    Alvarado JA, Wood I, Polansky JR. Human trabecular cells - II. Growth pattern and ultrastructural characteristics. Invest Ophthalmol Vis Sci. 1982;23:464–478.PubMedGoogle Scholar
  3. 3.
    Grierson I, Lee WR. Pressure-induced changes in the ultrastructure of the endothelium lining of Schlemm’s canal. Am J Ophthalmol. 1975;80(5):863–884.PubMedGoogle Scholar
  4. 4.
    Grierson I, Lee WR. The fine structure of the trabecular meshwork at graded levels of intraocular pressure. (1) Pressure effects within the near-physiological range (8-30 mmHg). Exp Eye Res. 1975;20(6):505–521.CrossRefPubMedGoogle Scholar
  5. 5.
    Montserrat C, Liton PB, Clahha P, Epstein DL, Gonzalez P. Effects fo donor age on proteasome activity and senescence in trabecular meshwork cells. Biochem Biophys Res Commun. 2004;323(22):1048–1054.Google Scholar
  6. 6.
    Epstein DL, Freddo TF, Bassett-Chu S, Chung M, Karageuzian L. Influence of ethacrynic acid on outflow facility in the monkey and coif eye. Invest Ophthalmol Vis Sci. 1987;28(12):2067–2075.PubMedGoogle Scholar
  7. 7.
    Stone M, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275:668–670.CrossRefPubMedGoogle Scholar
  8. 8.
    Rezaie T, Child A, Hitchings R, et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science. 2002;295:1077–1079.CrossRefPubMedGoogle Scholar
  9. 9.
    Wang N, Chitala SK, Fini ME, Schuman JS. Activation of tissue-specific stress response in the aqueous outfly pathway of the eye defines the glaucoma disease phenotype. Nat Med. 2001;7:304–309.CrossRefPubMedGoogle Scholar
  10. 10.
    Nolan MJ, Giovingo MC, Miller AM, et al. Aqueous humor sCD44 concentration and visual field loss in primary open-angle glaucoma. J Glaucoma. 2007;16(5):419–429.CrossRefPubMedGoogle Scholar
  11. 11.
    Luna C, Li G, Liton PB, et al. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol. 2009;47(1):198–204.CrossRefPubMedGoogle Scholar
  12. 12.
    Wirtz MK, Samples JR, Hong X, Severson T, Acott TS. Expression profile and genome location of CDNA clones from an infant human trabecular meshwork cell library. Invest Ophthalmol Vis Sci. 2002;43:3698–3704.PubMedGoogle Scholar
  13. 13.
    Knepper AP, Miller AM, Choi J, et al. Hyperphosphorylation of aqueous humor sCD44 anad primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2005;46:2829–2837.CrossRefPubMedGoogle Scholar
  14. 14.
    Samples JR, Alexander PA, Acott TS. Regulation of human trabecular meshwork metalloproteinase and inhibitors by interlukin-1 and dexamethasone. Invest Ophthalmol Vis Sci. 1993;34(12):3386–3395.PubMedGoogle Scholar
  15. 15.
    Rosenbaum JT, Samples JR, Hefender SH, Howes EL. Ocular inflammatory effects of intravitreal interleukin-1. Arch Ophthalmol. 1986;105:1117–1120.Google Scholar
  16. 16.
    Parshley DE, Bradley JM, Fisk A, et al. Laser trabeculoplasty induces stromelysin expression by trabecular juxtacanalicular cells. Invest Ophthalmol Vis Sci. 1996;37:795–804.PubMedGoogle Scholar
  17. 17.
    Bradley JMB, Anderssohn AM, Colvis CM, et al. Mediation of laser trabeculoplasty-induced matrix metalloproteinase expression by IL-1b and TNFa. Invest Ophthalmol Vis Sci. 2000;41:422–430.PubMedGoogle Scholar
  18. 18.
    Wang N, Chintala SK, Fini ME, Shuman JS. Ultrasound activates the TM ELAM-1/IL-1/NF-kB response: a potential mechanism for intraocular pressure reduction after phacoemulsification. Invest Ophthalmol Vis Sci. 2003;44:1977–1981.CrossRefPubMedGoogle Scholar
  19. 19.
    Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res. 2008;86(4):543–561.CrossRefPubMedGoogle Scholar
  20. 20.
    Keller KE, Aga M, Bradeley JM, Kelley MJ, Acott TS. Extracellular matrix turnover and outflow resisitance. Exp Eye Res. 2009;88(4):676–682.CrossRefPubMedGoogle Scholar
  21. 21.
    Johnstone MA, Grant WM. Pressure-dependent changes in structure of the aqueous outflow system in human and monkey eyes. Am J Ophthalmol. 1973;75:365–383.PubMedGoogle Scholar
  22. 22.
    Johnstone MA. A New Model Describes an Aqueous Outflow Pump and Causes of Pump Failure in Glaucoma. In: Grehn F, Weinreb RN, eds. Essentials in Ophthalmology: Glaucoma. Berlin: Springer; 2006.Google Scholar
  23. 23.
    Johnstone MA. Aqueous outflow: the case for a new model - moving fluid out of the eye may be the work of a biomechanical pump. Rev Ophthalmol. 2007;14.Google Scholar
  24. 24.
    Stamer WD, Peppel K, O’Donnell MS, Roberts BC, Wu F, Epstein DL. Expression of aquaporin-1 in human trabecular meshwork cells: role in resting cell volume. Invest Ophthalmol Vis Sci. 2001;42:1803–1811.PubMedGoogle Scholar
  25. 25.
    Chatterton JE, Patil RV, Sharif N, Clark AF, Wax MB. (Agent, Alcon) RNAi-mediated inhibition of aquaporin 4 for treatment of iop-related conditions. USA Patent Pending, application #20080214486. Applied for in 2008.Google Scholar
  26. 26.
    Fautsch MP, Johnson DH, and the Second ARVO/Pfizer Research Institute Working. Aqueous humor outflow: what do we know? Where will it lead us? Invest Ophthalmol Vis Sci. 2006;47:4181–4187.CrossRefPubMedGoogle Scholar
  27. 27.
    Fautsch MP, Bahler CK, Vrabel AM, et al. Perfusion of his-tagged eukaryotic myocilin increases outflow resistance in human anterior segments in the presence of aqueous humor. Invest Ophthalmol Vis Sci. 2006;47:213–221.CrossRefPubMedGoogle Scholar
  28. 28.
    Battista SA, Lu Z, Hofmann S, Freddo TF, Overby D, Gong H. Acute IOP elevation reduces the available area for aqueous humor outflow and induces herniations into the collector channels of bovine eyes. Invest Ophthalmol Vis Sci. 2008;49:5346–5352.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • John R. Samples
    • 1
    • 2
    • 3
  1. 1.Oregon Health and Sciences UniversityPortlandUSA
  2. 2.Rocky Vista UniversityParkerUSA
  3. 3.Pacific Coast Oto-Ophthalmology Society Specialty Eye CareParkerUSA

Personalised recommendations