Advertisement

Genetic Insights into Primary Open-Angle Glaucoma

  • Louis R. PasqualeEmail author
Chapter
Part of the Advances in Visual Science and Eye Diseases book series (AVSED, volume 1)

Abstract

Primary open-angle glaucoma (POAG) is a public cause problem with a projected prevalence of 110 million patients overall by 2040; 40 million of these cases will come from Asia [1]. Therefore a deeper understanding of this disease is an urgent challenge as treatments that address the root cause of POAG are needed. POAG is a seemingly enigmatic disease. The intraocular pressure (IOP) may or may not be elevated. If IOP is elevated, anterior segment examination does not reveal clues as to why this is the case. The optic nerve is excavated and pale, and there is attendant VF loss (Fig. 44.1). Genomics offers an incredible opportunity to gain insights into this IOP-related otherwise idiopathic optic neuropathy.

References

  1. 1.
    Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. 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.
    Teikari JM. Genetic factors in open-angle (simple and capsular) glaucoma. A population-based twin study. Acta Ophthalmol (Copenh). 1987;65(6):715–20.CrossRefGoogle Scholar
  3. 3.
    Bailey JN, Loomis SJ, Kang JH, et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet. 2016;48(2):189–94.CrossRefGoogle Scholar
  4. 4.
    Springelkamp H, Mishra A, Hysi PG, et al. Meta-analysis of genome-wide association studies identifies novel loci associated with optic disc morphology. Genet Epidemiol. 2015;39(3):207–16.CrossRefGoogle Scholar
  5. 5.
    Springelkamp H, Hohn R, Mishra A, et al. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun. 2014;5:4883.CrossRefGoogle Scholar
  6. 6.
    Hysi PG, Cheng CY, Springelkamp H, et al. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nat Genet. 2014;46(10):1126–30.CrossRefGoogle Scholar
  7. 7.
    Lu Y, Vitart V, Burdon KP, NEIGHBOR consortium. GWAS on central corneal thickness identifies a total of 27 associated loci, including six risk loci for keratoconus. Nat Genet. 2012;45(2):155–63.CrossRefGoogle Scholar
  8. 8.
    Pasquale LR, Loomis SJ, Kang JH, et al. CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States. Am J Ophthalmol. 2013;155(2):342–53. e345CrossRefGoogle Scholar
  9. 9.
    Burdon KP, Crawford A, Casson RJ, et al. Glaucoma risk alleles at CDKN2B-AS1 are associated with lower intraocular pressure, normal-tension glaucoma, and advanced glaucoma. Ophthalmology. 2012;119(8):1539–45.CrossRefGoogle Scholar
  10. 10.
    Gao S, Jakobs TC. Mice homozygous for a deletion in the glaucoma susceptibility locus INK4 show increased vulnerability of retinal ganglion cells to elevated intraocular pressure. Am J Pathol. 2016;186(4):985–1005.CrossRefGoogle Scholar
  11. 11.
    Altshuler DM, Gibbs RA, Peltonen L, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–8.CrossRefGoogle Scholar
  12. 12.
    Pasmant E, Sabbagh A, Vidaud M, Bieche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2011;25(2):444–8.CrossRefGoogle Scholar
  13. 13.
    Iglesias AI, Springelkamp H, Ramdas WD, Klaver CC, Willemsen R, van Duijn CM. Genes, pathways, and animal models in primary open-angle glaucoma. Eye (Lond). 2015;29(10):1285–98.CrossRefGoogle Scholar
  14. 14.
    Kang JH, Loomis SJ, Yaspan BL, et al. Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond). 2014;28(6):662–71.CrossRefGoogle Scholar
  15. 15.
    Buys ES, Ko YC, Alt C, et al. Soluble guanylate cyclase alpha1-deficient mice: a novel murine model for primary open angle glaucoma. PLoS One. 2013;8(3):e60156.CrossRefGoogle Scholar
  16. 16.
    Thorleifsson G, Walters GB, Hewitt AW, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet. 2010;42(10):906–9.CrossRefGoogle Scholar
  17. 17.
    Wiggs JL, Hee Kang J, Yaspan BL, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA. Hum Mol Genet. 2011;20(23):4707–13.CrossRefGoogle Scholar
  18. 18.
    Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. Netarsudil increases outflow facility in human eyes through multiple mechanisms. Invest Ophthalmol Vis Sci. 2016;57(14):6197–209.CrossRefGoogle Scholar
  19. 19.
    Kaufman PL. Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension. Expert Opin Pharmacother. 2017;18(4):433–44.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyIcahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations