Science: Glaucoma: Novel antifibrotic therapeutics for the trabecular meshwork
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15 months ago
david 4.3k
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Elevated intraocular pressure (IOP) remains the number one treatment focus in nearly all types of glaucoma. IOP is regulated, in part, by the trabecular meshwork (TM). An emerging area of focus in the development of new treatments for glaucoma involves novel antifibrotic therapeutics that target the TM.

Understanding the Role of Trabecular Meshwork and Fibrosis in Glaucoma

The trabecular meshwork is a critical regulator of intraocular pressure, primarily by controlling the outflow of aqueous humor -- the clear fluid filling the space in the front of the eyeball. In a healthy eye, this fluid is produced and drained at a rate that maintains a stable IOP. However, in glaucoma, decreased functionality of the TM can lead to increased resistance to fluid outflow, resulting in a rise in IOP. Over time, this increase in pressure can cause damage to the optic nerve.

One key process that can impair the function of the TM is fibrosis. Normally a reparative process characterized by the deposition of extracellular matrix components and contractile myofibroblasts, fibrosis can go astray and contribute to the pathogenesis of primary open-angle glaucoma (POAG) as well as the failure of minimally invasive glaucoma surgery (MIGS) devices when it becomes uncontrolled or excessive.

Fibrosis

Normally, fibrosis is a response to injury or damage and serves as a protective strategy to isolate and repair the injured area. However, when fibrosis becomes uncontrolled or excessive, it can interfere with normal organ function.

Fibroblasts, a type of cell involved in wound healing, produce collagen and other extracellular matrix proteins to form a scaffold for new tissue growth. Once the wound is healed, the fibroblasts retreat, and the excess collagen is broken down and removed.

This normal process can become disrupted, as in the case of hypertensive glaucoma. In general, fibroblasts may not retreat, or they may transform into a more permanent, contractile form called a myofibroblast. The excess collagen and other matrix proteins are not efficiently removed, resulting in a buildup that forms fibrous, scar-like tissue. Over time, this can disrupt the normal function of the TM, or any other organ involved in the general case of fibrosis.

A key statement from this study caught my attention:

“Fibrosis in the TM tissue can adversely affect the implanted stents and is the main cause of failure in MIGS (Luo et al., 2022). Antifibrotic therapeutics targeting the TM thus represent a promising strategy in glaucoma management by reducing IOP and improving the surgical success rates of MIGS devices.

The Promise of Antifibrotic Therapies

Antifibrotic therapies represent a new and promising approach in glaucoma treatment. By specifically targeting the fibrotic processes within the TM, these therapies aim to restore normal aqueous humor outflow and thus maintain a healthy IOP. Current research delves into the antifibrotic mechanisms of these therapies, their efficacy in mitigating the pathogenic effects of fibrosis, and progress from pre-clinical to clinical studies.

This represents a groundbreaking shift from the traditional therapeutic strategies that primarily focused on reducing IOP either by decreasing aqueous humor production or enhancing its outflow through alternative pathways. Antifibrotic therapies have the potential to tackle the root cause -- fibrosis -- which interferes with the natural function of the TM, thereby causing an elevated IOP.

I am very excited about this area of research.

Study Abstract

Glaucoma is a chronic and progressive neurodegenerative disease characterized by the loss of retinal ganglion cells and visual field defects, and currently affects around 1% of the world's population. Elevated intraocular pressure (IOP) is the best-known modifiable risk factor and a key therapeutic target in hypertensive glaucoma. The trabecular meshwork (TM) is the main site of aqueous humor outflow resistance and therefore a critical regulator of IOP. Fibrosis, a reparative process characterized by the excessive deposition of extracellular matrix components and contractile myofibroblasts, can impair TM function and contribute to the pathogenesis of primary open-angle glaucoma (POAG) as well as the failure of minimally invasive glaucoma surgery (MIGS) devices. This paper provides a detailed overview of the current anti-fibrotic therapeutics targeting the TM in glaucoma, along with their anti-fibrotic mechanisms, efficacy as well as the current research progress from pre-clinical to clinical studies.

Keywords: Fibrosis; Glaucoma; MIGS; Trabecular meshwork.

glaucoma trabecular-meshwork fibrosis anti-fribrotic-therapy • 567 views
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