An overview of human pluripotent stem cell applications for the understanding and treatment of blindness
John Ravenscroft in The Routledge Handbook of Visual Impairment, 2019
The trabecular meshwork is a small area of cells surrounded by extracellular matrix, located at the base of the cornea, close to the ciliary body. Functioning as the drainage system of the eye, the trabecular meshwork actively redistributes fluid from the anterior chamber of the eye to Schlemm’s canal to maintain intraocular pressure. Additionally, the trabecular meshwork phagocytoses debris, an important feature of the maintenance of healthy aqueous humor and its clearance system. If the trabecular meshwork is inoperable or poorly functioning and regular homeostatic regulation is lost, intraocular pressure rises, which can result in damage to the optic nerve. Therefore, defective functionality of the trabecular meshwork is thought to result in open-angle glaucoma, the most common form of glaucoma. Ding et al. (2014) co-cultured mouse iPSCs with immortalised human trabecular meshwork cells. This technique induces distinct morphological changes and generates iPSC-trabecular meshwork cells that resemble trabecular meshwork cells as described in the literature. Importantly, these cells also exhibit phagocytic functionality, a key feature of trabecular meshwork. hPSCs have been differentiated to trabecular meshwork-like cells by generation of embryoid bodies on trabecular meshwork extracellular matrix in a medium conditioned with meshwork (Abu-Hassan et al., 2015). Trabecular meshwork cells have been then transplanted into animal models of glaucoma, effectively restoring intraocular pressure and improving aqueous humor outflow facility (Abu-Hassan et al., 2015; Zhu et al., 2016; Zhu et al., 2017).
Eczema and the Eye
Donald Rudikoff, Steven R. Cohen, Noah Scheinfeld in Atopic Dermatitis and Eczematous Disorders, 2014
Glaucoma occurs as a complication of elevated intraocular pressure. Normal intraocular pressure depends on a balance between the production and outflow of the aqueous humor in the anterior segment of the eye. The function of aqueous humor is to maintain the shape of the eye and to provide nourishment to the lens and cornea. Aqueous humor is formed by the ciliary body in the posterior chamber. From there, it flows through the pupil to the anterior chamber. It leaves the anterior chamber through a sponge-like system of pores called the trabecular meshwork, located at the junction of the cornea and the root of the iris. The trabecular meshwork causes a resistance to flow and elevation of pressure. From the trabecular meshwork, fluid moves into the canal of Schlemm and then to the venous system. Under physiological conditions, a balance exists between fluid production and fluid outflow such that enough internal pressure is present to maintain the overall round shape of the eye. The normal intraocular pressure is 15 mmHg (Lens et al. 1999, Kaufman and Alm 2003). An elevation of intraocular pressure with no other abnormalities is known as ocular hypertension. Ocular hypertension associated with visual field defects or observable damage to the optic nerve is considered glaucoma.
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Anton C. de Groot in Monographs in Contact Allergy, 2021
Echothiophate is a potent, long-acting cholinesterase inhibitor with parasympathomimetic activity. Its iodide salt echothiophate iodide (CAS number 513-10-0, EC number 208-152-1, molecular formula C9H23INO3PS) potentiates the action of endogenous acetylcholine by inhibiting acetylcholinesterase that hydrolyzes acetylcholine. When applied topically to the eye, this agent prolongs stimulation of the parasympathetic receptors at the neuromuscular junctions of the longitudinal muscle of the ciliary body. Contraction of longitudinal muscle pulls on the scleral spur, and opens the trabecular meshwork, thereby increasing aqueous humor outflow from the eye and reducing intraocular pressure. Echothiopate iodide is indicated for use in the treatment of subacute or chronic angle-closure glaucoma after iridectomy or where surgery is refused or contraindicated (1).
Clinical Study of the IOPTx™ System - an Electroceutical Wearable to Lower Intraocular Pressure
Published in Current Eye Research, 2021
Jay V. Shah, Gabriel O. Albors, Jack Williams, Quan Yuan, Elena Milla, Murray I. Firestone, Gabriel Simón, Pedro P. Irazoqui
Glaucoma affected about 60.5 million people in 2010, 74% with open-angle glaucoma, of which 4.5 million will become blind; this number will rise to approximately 79.6 million in 2020, of which 5.9 million will become blind.1 Glaucoma stems from a buildup of intraocular pressure (IOP) in the anterior chamber of the eye, which mechanically constricts and damages the optic nerve, eventually leading to irreversible blindness. The most common type, primary open angle glaucoma, occurs due to an increased resistance of aqueous humor outflow with no discernible change in anterior chamber angle. The trabecular meshwork is an area of tissue in the eye, between the iris and the cornea, responsible for draining aqueous humor from the anterior chamber. The aqueous humor then passes through the Schlemm’s canal from where it then flows into the circulatory system. Oftentimes, in cases of open angle glaucoma, the individual has no symptoms or warning signs, and the disease gradually progresses leading to eventual blindness.2
Simvastatin Attenuates Glucocorticoid-Induced Human Trabecular Meshwork Cell Dysfunction via YAP/TAZ Inactivation
Published in Current Eye Research, 2023
Hannah Yoo, Ayushi Singh, Haiyan Li, Ana N. Strat, Tyler Bagué, Preethi S. Ganapathy, Samuel Herberg
The trabecular meshwork (TM) plays a central role in the conventional outflow pathway, which drains the aqueous humor from the anterior chamber to regulate outflow facility and intraocular pressure.1–3 The bidirectional interactions between TM cells4 and their extracellular matrix (ECM) are crucial for maintaining normal tissue function in the healthy eye.5,6 In primary open-angle glaucoma, the most common form of glaucoma,7 disruption of these interactions drive progressive fibrotic-like tissue remodeling. Key characteristics of this postulated process include increased TM contraction, actin stress fiber assembly, ECM deposition/crosslinking, and overall tissue stiffening.8 These pathologic alterations lead to increased outflow resistance driving ocular hypertension, which provides further feed-forward amplification and may ultimately push the TM to irreversibly fail.9,10 Despite substantial scientific efforts over the past several decades devoted to understanding TM pathophysiology, the mechanisms underlying persistent tissue dysfunction in glaucoma remain elusive.
Diabetic eye: associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment
Published in Expert Opinion on Drug Delivery, 2021
Axel Kattar, Angel Concheiro, Carmen Alvarez-Lorenzo
Glaucoma is the leading cause of blindness worldwide and is defined by damage of the retinal ganglion cells, leading to irreversible damage of the optic nerve [32]. This is often accompanied by a rise of the intraocular pressure (IOP) triggered through different mechanisms. Open-angle glaucoma is caused by blocking of the trabecular meshwork, which in turn hinders fluid drainage and increases pressure. This is the most common form of glaucoma and happens at slow pace. Angle closure glaucoma is provoked by the iris coming forward and blocking the drainage angle between the iris and the cornea. It can happen over time or suddenly. Secondary angle closure glaucoma, in which the angle can be opened or closed, is caused by a secondary factor that leads to drainage hindrance, for example excessive pigment release blocking the trabecular meshwork (pigmentary glaucoma). Although the role of diabetes is unclear, direct correlations were found between diabetes duration and fasting glucose levels and the increase in IOP [33].
Related Knowledge Centers
- Eye
- Cornea
- Ciliary Body
- Aqueous Humour
- Anterior Chamber of Eyeball
- Schlemm'S Canal
- Trabecula
- Elastin
- Ciliary Muscle
- Tendon