Normal-tension Glaucoma: Pathogenesis and Genetics

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2019 Jan 18

PMID 30651837

Citations 50

Authors

Alexandra Trivli

Ioannis Koliarakis

Chryssa Terzidou

George N Goulielmos

Charalambos S Siganos

Demetrios A Spandidos

Georgios Dalianis

Efstathios T Detorakis

Affiliations

Soon will be listed here.

Abstract

Normal-tension glaucoma (NTG) is a multifactorial optic neuropathy which, similar to open-angle glaucomas, is characterized by progressive retinal ganglion cell death and glaucomatous visual field loss. The major distinction of NTG from open-angle glaucomas is that the intraocular pressure (IOP) does not exceed the normal range. Missing the major risk factor and target of therapy, the elevated IOP, NTG poses a clinical challenge. Several insightful reviews have been published on the pathophysiology of NTG describing the possible underlying mechanisms. The current literature available also suggests that a significant percentage of patients with NTG (as high as 21%) have a family history of glaucoma, indicating a genetic predisposition to the disease. These facts strengthen the indication that NTG remains an enigmatic process. The aim of this review was to summarize the vascular, mechanical and genetic components considered to be responsible for NTG development and to discuss the mechanisms through which they are involved in the pathogenesis of NTG.

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References

Wirtz M, Samples J, Rust K, Lie J, Nordling L, Schilling K . GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36. Arch Ophthalmol. 1999; 117(2):237-41. DOI: 10.1001/archopht.117.2.237. View

Cioffi G, Sullivan P . The effect of chronic ischemia on the primate optic nerve. Eur J Ophthalmol. 1999; 9 Suppl 1:S34-6. DOI: 10.1177/112067219900901S12. View

Cursiefen C, Wisse M, Cursiefen S, Junemann A, Martus P, Korth M . Migraine and tension headache in high-pressure and normal-pressure glaucoma. Am J Ophthalmol. 2000; 129(1):102-4. DOI: 10.1016/s0002-9394(99)00289-5. View

Haefliger I, Flammer J, Beny J, Luscher T . Endothelium-dependent vasoactive modulation in the ophthalmic circulation. Prog Retin Eye Res. 2001; 20(2):209-25. DOI: 10.1016/s1350-9462(00)00020-3. View

Hofman P, Hoyng P, VanderWerf F, Vrensen G, Schlingemann R . Lack of blood-brain barrier properties in microvessels of the prelaminar optic nerve head. Invest Ophthalmol Vis Sci. 2001; 42(5):895-901. View

Drance S, Anderson D, Schulzer M . Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001; 131(6):699-708. DOI: 10.1016/s0002-9394(01)00964-3. View

Yuan L, Neufeld A . Activated microglia in the human glaucomatous optic nerve head. J Neurosci Res. 2001; 64(5):523-32. DOI: 10.1002/jnr.1104. View

Flammer J . [Glaucomatous optic neuropathy: a reperfusion injury]. Klin Monbl Augenheilkd. 2001; 218(5):290-1. DOI: 10.1055/s-2001-15883. View

Pache M, Krauchi K, Cajochen C, Wirz-Justice A, Dubler B, Flammer J . Cold feet and prolonged sleep-onset latency in vasospastic syndrome. Lancet. 2001; 358(9276):125-6. DOI: 10.1016/S0140-6736(01)05344-2. View

10.

Gherghel D, Orgul S, Gugleta K, Flammer J . Retrobulbar blood flow in glaucoma patients with nocturnal over-dipping in systemic blood pressure. Am J Ophthalmol. 2001; 132(5):641-7. DOI: 10.1016/s0002-9394(01)01193-x. View

11.

Buckley C, Hadoke P, Henry E, OBrien C . Systemic vascular endothelial cell dysfunction in normal pressure glaucoma. Br J Ophthalmol. 2002; 86(2):227-32. PMC: 1770997. DOI: 10.1136/bjo.86.2.227. View

12.

Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M . Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science. 2002; 295(5557):1077-9. DOI: 10.1126/science.1066901. View

13.

Flammer J, Orgul S, Costa V, Orzalesi N, Krieglstein G, Serra L . The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002; 21(4):359-93. DOI: 10.1016/s1350-9462(02)00008-3. View

14.

Pache M, Kaiser H, Akhalbedashvili N, Lienert C, Dubler B, Kappos L . Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis. Eur Neurol. 2003; 49(3):164-8. DOI: 10.1159/000069085. View

15.

Gugleta K, Orgul S, Hasler P, Picornell T, Gherghel D, Flammer J . Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci. 2003; 44(4):1573-80. DOI: 10.1167/iovs.02-0521. View

16.

Nicolela M, Ferrier S, Morrison C, Archibald M, LeVatte T, Wallace K . Effects of cold-induced vasospasm in glaucoma: the role of endothelin-1. Invest Ophthalmol Vis Sci. 2003; 44(6):2565-72. DOI: 10.1167/iovs.02-0913. View

17.

Tang S, Toda Y, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S . The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene. Hum Genet. 2003; 113(3):276-9. DOI: 10.1007/s00439-003-0964-y. View

18.

Galassi F, Sodi A, Ucci F, Renieri G, Pieri B, Baccini M . Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study. Arch Ophthalmol. 2003; 121(12):1711-5. DOI: 10.1001/archopht.121.12.1711. View

19.

Chauhan B, LeVatte T, Jollimore C, Yu P, Reitsamer H, Kelly M . Model of endothelin-1-induced chronic optic neuropathy in rat. Invest Ophthalmol Vis Sci. 2003; 45(1):144-52. DOI: 10.1167/iovs.03-0687. View

20.

Golubnitschaja O, Yeghiazaryan K, Liu R, Monkemann H, Leppert D, Schild H . Increased expression of matrix metalloproteinases in mononuclear blood cells of normal-tension glaucoma patients. J Glaucoma. 2004; 13(1):66-72. DOI: 10.1097/00061198-200402000-00013. View