Mechanisms of Glaucoma Development in Pseudoexfoliation Syndrome

Matrix Metalloproteinases and Their Inhibitors in Aqueous Humor of Patients with Pseudoexfoliation Syndrome/Glaucoma and Primary Open-Angle Glaucoma

“…19 In eyes with PEX syndrome and PEXG, the excess de novo production of various extracellular matrix components results in a progressive accumulation of an abnormal fibrillar material in most anterior segment tissues, including the juxtacanalicular region of the trabecular meshwork. 1,2,8,9 The findings of this study suggest that both the reduced levels of activated MMP-2 and the significantly increased concentrations of TIMP-1 and -2 leading to a stoichiometric excess of TIMP-2 over MMP-2 in aqueous humor from PEXG eyes are causally related to inappropriate matrix degradation and progressive matrix accumulation. A decreased degradability of PEX material from increased cross-linking processes preventing access of proteases or MMP activators may further play a role.…”

“…6,7 Active involvement of the trabecular meshwork in this abnormal matrix process leading to progressive accumulation of PEX material in the juxtacanalicular tissue is considered to be the primary cause of chronic pressure elevation in eyes with PEX syndrome. 8,9 However, the mechanisms responsible for this aberrant matrix process remain unknown. Excessive production and accumulation of abnormal matrix components may be due to increased de novo synthesis, decreased turnover of matrix components, or both.…”

Inhibitory and Agonistic Autoantibodies Directed Against the β2-Adrenergic Receptor in Pseudoexfoliation Syndrome and Glaucoma

“…PEX material consists of fibrillar aggregates containing elastic fiber components such as elastin, fibrillin-1, fibulin, microfibrilassociated glycoprotein-1 (MAGP-1), latent transforming growth factor β (LTBP)1/2, and cross-linking enzymes such as lysyl oxidase-like 1 (LOXL1) (Schlotzer-Schrehardt et al, 2000;Krumbiegel et al, 2009;Lee et al, 2009;Zenkel and Schlotzer-Schrehardt, 2014;Founti et al, 2015), which can accumulate in the trabecular meshwork, the main outflow pathway of the eye, and may reduce the outflow of aqueous humor and increased intraocular pressure (IOP) (Johnson and Brubaker, 1982). Consequently, PEXS is strongly associated with the development of PEX glaucoma (PEXG) (Schlotzer-Schrehardt et al, 2002;Anastasopoulos et al, 2015). The latter is the most common type of secondary open-angle glaucoma (SOAG) (Ritch, 2001).…”

“…The pathophysiology of PEXS and PEXG is still elusive (Anastasopoulos et al, 2015;Schlotzer-Schrehardt and Khor, 2021). It is widely assumed that a generalized elastosis, induced by stress, is the principal process in the pathophysiology of PEXS (Schlotzer-Schrehardt et al, 2002;Anastasopoulos et al, 2015;Schlotzer-Schrehardt and Khor, 2021). Transforming growth factor β1 (TGF-β1), being increased in aqueous humor of PEXG and PEXS, and oxidative stress were considered to be the main contributors to the disease (Schlotzer-Schrehardt et al, 2001;Schlotzer-Schrehardt, 2010).…”

Estudio genético del síndrome pseudoexfoliativo

“…Los agregados de material pseudoexfoliativo presentes en el ángulo iridocorneal pueden comportarse también como un nidus para una acumulación no específica de proteínas séricas. Estudios con inmunohistoquímica han detectado un incremento significativo de la cantidad de albúmina presente a nivel de la malla trabecular en ojos con SPEX, lo que teóricamente podría contribuir al incremento de la PIO [157,158].…”