Pathogenesis of Glaucoma: Extracellular Matrix Dysfunction in the Trabecular Meshwork-A Review

Overview

Journal Clin Exp Ophthalmol

Specialty Ophthalmology

Date 2022 Jan 17

PMID 35037377

Authors

Kate E Keller

Donna M Peters

Affiliations

Soon will be listed here.

Abstract

The trabecular meshwork regulates aqueous humour outflow from the anterior chamber of the eye. It does this by establishing a tunable outflow resistance, defined by the interplay between cells and their extracellular matrix (ECM) milieu, and the molecular interactions between ECM proteins. During normal tissue homeostasis, the ECM is remodelled and trabecular cell behaviour is modified, permitting increased aqueous fluid outflow to maintain intraocular pressure (IOP) within a relatively narrow physiological pressure. Dysfunction in the normal homeostatic process leads to increased outflow resistance and elevated IOP, which is a primary risk factor for glaucoma. This review delineates some of the changes in the ECM that lead to gross as well as some more subtle changes in the structure and function of the ECM, and their impact on trabecular cell behaviour. These changes are discussed in the context of outflow resistance and glaucoma.

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References

Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S . FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling. Sci Transl Med. 2014; 6(232):232ra50. PMC: 4414050. DOI: 10.1126/scitranslmed.3008264. View

Haddadin R, Oh D, Kang M, Villarreal Jr G, Kang J, Jin R . Thrombospondin-1 (TSP1)-null and TSP2-null mice exhibit lower intraocular pressures. Invest Ophthalmol Vis Sci. 2012; 53(10):6708-17. PMC: 3462480. DOI: 10.1167/iovs.11-9013. View

Acott T, Kingsley P, Samples J, Van Buskirk E . Human trabecular meshwork organ culture: morphology and glycosaminoglycan synthesis. Invest Ophthalmol Vis Sci. 1988; 29(1):90-100. View

Liu X, Wu H, Byrne M, Jeffrey J, Krane S, Jaenisch R . A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. J Cell Biol. 1995; 130(1):227-37. PMC: 2120510. DOI: 10.1083/jcb.130.1.227. View

Hann C, Bahler C, Johnson D . Cationic ferritin and segmental flow through the trabecular meshwork. Invest Ophthalmol Vis Sci. 2004; 46(1):1-7. DOI: 10.1167/iovs.04-0800. View

Bailey A, Paul R, Knott L . Mechanisms of maturation and ageing of collagen. Mech Ageing Dev. 1999; 106(1-2):1-56. DOI: 10.1016/s0047-6374(98)00119-5. View

Narizhneva N, Byers-Ward V, Quinn M, Zidar F, Plow E, Topol E . Molecular and functional differences induced in thrombospondin-1 by the single nucleotide polymorphism associated with the risk of premature, familial myocardial infarction. J Biol Chem. 2004; 279(20):21651-7. PMC: 1459418. DOI: 10.1074/jbc.M311090200. View

Schlotzer-Schrehardt U, Zenkel M, Kuchle M, Sakai L, Naumann G . Role of transforming growth factor-beta1 and its latent form binding protein in pseudoexfoliation syndrome. Exp Eye Res. 2002; 73(6):765-80. DOI: 10.1006/exer.2001.1084. View

Inatani M, Tanihara H, Katsuta H, Honjo M, Kido N, Honda Y . Transforming growth factor-beta 2 levels in aqueous humor of glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol. 2001; 239(2):109-13. DOI: 10.1007/s004170000241. View

10.

Hamanaka T, Kimura M, Sakurai T, Ishida N, Yasuda J, Nagasaki M . A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients. Invest Ophthalmol Vis Sci. 2017; 58(5):2818-2831. DOI: 10.1167/iovs.16-20646. View

11.

Raghunathan V, Morgan J, Park S, Weber D, Phinney B, Murphy C . Dexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and Matrix. Invest Ophthalmol Vis Sci. 2015; 56(8):4447-59. PMC: 4509060. DOI: 10.1167/iovs.15-16739. View

12.

Kuchtey J, Kuchtey R . The microfibril hypothesis of glaucoma: implications for treatment of elevated intraocular pressure. J Ocul Pharmacol Ther. 2014; 30(2-3):170-80. PMC: 3991966. DOI: 10.1089/jop.2013.0184. View

13.

Gong H, Freddo T, Johnson M . Age-related changes of sulfated proteoglycans in the normal human trabecular meshwork. Exp Eye Res. 1992; 55(5):691-709. DOI: 10.1016/0014-4835(92)90174-q. View

14.

Bredrup C, Matejas V, Barrow M, Blahova K, Bockenhauer D, Fowler D . Ophthalmological aspects of Pierson syndrome. Am J Ophthalmol. 2008; 146(4):602-611. DOI: 10.1016/j.ajo.2008.05.039. View

15.

Wu Y, La Pierre D, Wu J, Yee A, Yang B . The interaction of versican with its binding partners. Cell Res. 2005; 15(7):483-94. DOI: 10.1038/sj.cr.7290318. View

16.

Schlotzer-Schrehardt U, Pasutto F, Sommer P, Hornstra I, Kruse F, Naumann G . Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients. Am J Pathol. 2008; 173(6):1724-35. PMC: 2626384. DOI: 10.2353/ajpath.2008.080535. View

17.

Robertson J, Golesic E, Gauldie J, West-Mays J . Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats. Invest Ophthalmol Vis Sci. 2009; 51(1):308-18. DOI: 10.1167/iovs.09-3380. View

18.

Mercado M, Nur-E-Kamal A, Liu H, Gross S, Movahed R, Meiners S . Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin. J Neurosci. 2004; 24(1):238-47. PMC: 6729556. DOI: 10.1523/JNEUROSCI.4519-03.2004. View

19.

Ethier C, Chan D . Cationic ferritin changes outflow facility in human eyes whereas anionic ferritin does not. Invest Ophthalmol Vis Sci. 2001; 42(8):1795-802. View

20.

Gabelt B, Kaufman P . Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res. 2005; 24(5):612-37. DOI: 10.1016/j.preteyeres.2004.10.003. View