Trabecular Meshwork and Intraocular Pressure Dynamics: Oxidative Stress‐Induced Changes

Abstract

Glaucoma is known as progressive neurodegenerative disease with irreversible loss of vision. Next to perimetric visual field defects, morphological alterations of the optic nerve and an increased intraocular pressure (IOP) occur. IOP is a fine regulated, complex homeostasis of production of aqueous humor (AH) in the non-pigmented ciliary body and its outflow. About 80% of AH is drained throughout the trabecular meshwork (TM). Any outflow resistance, with consecutive increase in IOP, can be generated by a decreased pore size or any other alterations of TM, making it more rigid. Oxidative stress, a disbalance of oxidants and antioxidants, is one mechanism, causing an altered extracellular matrix (ECM), and seems to play a key role in the pathogenesis of glaucomatous nerve atrophy. Damage of DNA, caused by oxidative stress, was shown in TM cells of glaucoma patients. This chapter gives a review about oxidative stress and its pathological alterations in the main outflow pathway-the trabecular meshworkin glaucoma patients.

Interplay between Oxidative Stress, Inflammation, and Amyloidosis in the Anterior Segment of the Eye; Its Pathological Implications

“…Its inner face borders the anterior chamber, and the outside lies against the corneal stroma, sclera, and Schlemm's canal. The TM consists of connective tissue surrounded by endothelium and consists of two parts: the nonfiltering portion, occupied by trabecular cells, and the filtering portion [61,62]. Trabecular cells are aggressive phagocytic cells responsible for removing cell debris and proteins from the aqueous humor.…”

“…Trabecular cells are aggressive phagocytic cells responsible for removing cell debris and proteins from the aqueous humor. The filtering portion is composed by the cribriform layer, the corneoscleral meshwork, and the uveal meshwork [61,62].…”

“…The TM and related outflow pathways remove the aqueous humor from the anterior chamber of the eye. The intraocular pressure depends on the rate of fluid removal by the TM [61,63]. In normal conditions, the rate of fluid removal matches the rate of its formation, but when the TM cannot keep up with the rate of fluid formation the intraocular pressure becomes elevated, which is a major risk for glaucoma, oxidative damage can result even in specific molecular changes that contribute to the development of age-related sight-threatening diseases, such as glaucoma and cataracts [3,62,63].…”

“…The extracellular matrix material that accumulates is composed by glycosaminoglycans and proteoglycans, myocilin, thrombospondin, fibronectin, and colchicine [10,60]. Moreover, the properties of the extracellular materials change with an increase in the deposition of electron-dense plaques [61]. Extracellular matrix deposition, OS, and TGF-β signaling pathways are certainly important components of glaucoma pathogenesis, and altogether can induce cell death, extracellular matrix production, and accelerated senescence [2].…”