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Nikhil Prasad  Fact checked by:Thailand Medical News Team Sep 07, 2024  3 months, 2 weeks, 2 days, 8 hours, 28 minutes ago

A new approach to combat Glaucoma's tissue stiffness by targeting Alpha-v Beta-3 Integrin

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A new approach to combat Glaucoma's tissue stiffness by targeting Alpha-v Beta-3 Integrin
Nikhil Prasad  Fact checked by:Thailand Medical News Team Sep 07, 2024  3 months, 2 weeks, 2 days, 8 hours, 28 minutes ago
Glaucoma News: Understanding Glaucoma and Its Impact on Vision
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is a progressive optic neuropathy, meaning it involves damage to the optic nerve over time. This damage results in vision loss, and unfortunately, once vision is lost, it cannot be restored. A critical factor contributing to the progression of glaucoma is the stiffening of the lamina cribrosa (LC), a mesh-like structure in the optic nerve head (ONH). As this tissue becomes stiffer, it affects the ability of retinal ganglion cells to transmit visual information to the brain, leading to vision impairment.


A new approach to combat Glaucoma's tissue stiffness by targeting Alpha-v Beta-3 Integrin

This Glaucoma News report will explore how a specific protein, called αVβ3 (Alpha-v Beta-3) integrin, plays a crucial role in this process of stiffening and how recent research aims to target this protein to potentially slow down or halt the progression of glaucoma. Researchers from University College Dublin and Mater Misericordiae University Hospital, both in Dublin, Ireland, have focused their efforts on better understanding the connection between αVβ3 integrin and tissue stiffness in glaucoma patients.
 
The Link Between αVβ3 Integrin and Glaucoma
Integrins are proteins that sit on the surface of cells, acting as a bridge between the cells and the surrounding environment. They help cells communicate with their surroundings, influencing a wide range of cellular functions, including cell growth, movement, and the production of the extracellular matrix (ECM), which gives tissues their structure. In glaucoma, the lamina cribrosa becomes stiffer due to an increase in ECM proteins, which leads to tissue remodeling. One specific integrin, αVβ3, has been found to play a significant role in this stiffening process.
 
In the recent study, researchers examined the expression levels of αVβ3 integrin in cells from glaucoma patients and compared them to cells from healthy individuals. They discovered that αVβ3 integrin levels were significantly higher in glaucoma patients. This finding suggests that the increased levels of this integrin may be contributing to the abnormal accumulation of ECM and the resulting tissue stiffness seen in glaucoma.
 
Testing the Impact of Blocking αVβ3 Integrin
Given the elevated levels of αVβ3 integrin in glaucoma patients, the research team hypothesized that blocking this protein might reduce tissue stiffness and slow down the progression of glaucoma. To test this hypothesis, they used two methods to inhibit αVβ3 integrin: cilengitide, a known αVβ3 integrin inhibitor, and siRNA, a genetic tool that silences the production of specific proteins.
 
Their experiments were conducted on cells from both healthy individuals and glaucoma patients. By treating these cells with cilengitide or siRNA, the researchers were able to reduce the levels of αVβ3 integrin. Importantly, this reduction in integrin levels was associated with a decrease in the production of ECM proteins, such as collagen and fibronectin, which are known to contribute to tissue stiffness.
 
The study findings showed that in glaucoma cells, cilengitide treatment significantly reduced αVβ3 integrin levels, leading to lower ECM production and a decrease in tissue stiffness. This result provides strong evidence that targeting αVβ3 integrin could be a promising therapeutic approach for glaucoma.
 
The Role of αVβ3 Integrin in Tissue Stiffness
The research highlighted the role of αVβ3 integrin in mechanotransduction, a process where cells sense and respond to mechanical changes in their environment. In glaucoma, the lamina cribrosa undergoes mechanical stress due to increased intraocular pressure, causing cells to produce more ECM proteins and further stiffen the tissue. This stiffening creates a vicious cycle, where increased stiffness leads to more ECM production, worsening the condition.

By blocking αVβ3 integrin, researchers were able to disrupt this cycle, reducing both ECM production and tissue stiffness. This finding suggests that αVβ3 integrin is not only a marker of tissue stiffness in glaucoma but also a key driver of the disease's progression.
 
Potential for Anti-Fibrotic Therapies
The results of this study open the door to the development of new anti-fibrotic therapies for glaucoma. Current treatments for glaucoma focus on lowering intraocular pressure, but these therapies do not address the underlying issue of tissue stiffness. Targeting αVβ3 integrin offers a new approach that could complement existing treatments by directly addressing the stiffness of the lamina cribrosa.
 
Cilengitide, the drug used in this study, has already been tested in other conditions, such as cancer, where tissue stiffness plays a role. Its potential use in glaucoma represents an exciting avenue for future research and drug development. By inhibiting αVβ3 integrin, cilengitide could reduce tissue stiffness and slow down the progression of glaucoma, offering new hope for patients who do not respond to traditional pressure-lowering treatments.
 
Study Conclusions
This groundbreaking study demonstrates the importance of αVβ3 integrin in the progression of glaucoma. By targeting this protein, researchers were able to reduce the production of ECM proteins and decrease tissue stiffness in cells from glaucoma patients. These findings suggest that αVβ3 integrin is a promising target for new therapies that could slow down or even halt the progression of glaucoma.
 
The study's authors highlight the need for further research to explore the potential of αVβ3 integrin inhibitors like cilengitide in clinical settings. While the current study was conducted on cells in the laboratory, the next step will be to test these findings in animal models and eventually in human clinical trials.
 
The study findings were published in the peer-reviewed journal: Cells.
https://www.mdpi.com/2073-4409/13/17/1487
 
For the latest Glaucoma News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/plasma-lactoferrin-levels-a-new-biomarker-for-glaucoma-severity
 
https://www.thailandmedical.news/news/study-finds-that-consumption-of-ultra-processed-foods-increases-risk-of-glaucoma
 
https://www.thailandmedical.news/articles/glaucoma-news

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