Illustration of matrix contraction in the eye, with FAK inhibitors.

Matrix Contraction: Unlocking New Treatments for Eye Disease?

Lena Voss in Health & Wellness December 2025 • 3 min read.

"Could FAK Family Inhibition Hold the Key to Preventing Vision Loss?"

Fibrosis, characterized by excessive tissue buildup and contraction, can severely impair organ function. In the eye, this process leads to the formation of epiretinal membranes (ERMs), essentially fibrotic scars that distort vision and can cause significant vision loss. These membranes contract, disrupting the delicate architecture of the retina.

Müller cells, a type of glial cell in the retina, play a critical role in this process. These cells can transform into myofibroblasts, cells with contractile properties, and are found within ERMs. Understanding how these cells contribute to ERM contraction is crucial for developing effective therapies.

Researchers have previously shown that dasatinib, a drug that inhibits Src-family kinases and Abl kinase, can prevent matrix contraction in Müller cells. This finding opens the door to exploring other molecules involved in this pathway, offering hope for new treatments.

What is Matrix Contraction and Why Should You Care?

Illustration of matrix contraction in the eye, with FAK inhibitors.

Matrix contraction occurs when cells exert force on the surrounding extracellular matrix, causing it to shrink and condense. In the eye, this contraction can distort the retina, leading to blurred vision, metamorphopsia (distorted images), and even retinal detachment. Conditions like macular hole, macular pucker, proliferative vitreoretinopathy (PVR), and proliferative diabetic retinopathy (PDR) are all associated with ERMs and matrix contraction.

Researchers at the University of Louisville investigated the role of the FAK family of proteins in this process, focusing on FAK (focal adhesion kinase) and PYK2. Here’s what they uncovered:

Dasatinib's Impact: Dasatinib, known to inhibit Src-family kinases (SFKs) and Abl kinase, significantly reduces tyrosine phosphorylation of FAK and PYK2, suggesting these kinases are downstream targets.
Targeting FAK and PYK2: Inhibitors PF431396 (FAK/PYK2 dual inhibitor) and PF573228 (FAK inhibitor) effectively reduced matrix contraction in Müller cells.
Hic-5's Role: Both dasatinib and PF431396 reduced phosphorylation of Hic-5, a protein involved in cell signaling and focal adhesions, suggesting it acts downstream of the FAK family.

These findings suggest that FAK family members are key players in matrix contraction by transdifferentiated Müller cells, with Hic-5 situated downstream within the signaling pathway. Understanding this complex interplay offers new targets for therapeutic intervention.

Future Implications: A Brighter Outlook for Vision?

These research findings highlight the potential of targeting FAK/PYK2 to reduce the incidence of vision loss from ERMs associated with various eye diseases. As several FAK/PYK2 inhibitors are already being developed and tested for cancer treatment, repurposing or adapting these drugs for ocular conditions could offer a new therapeutic avenue. Further research is needed, but the future looks promising.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.exer.2017.08.010, Alternate LINK

Title: Focal Adhesion Kinase Family Is Involved In Matrix Contraction By Transdifferentiated Müller Cells

Subject: Cellular and Molecular Neuroscience

Journal: Experimental Eye Research

Publisher: Elsevier BV

Authors: Rintaro Tsukahara, Kazuhiko Umazume, Kevin Mcdonald, Henry J. Kaplan, Shigeo Tamiya

Published: 2017-11-01

Everything You Need To Know

What is matrix contraction in the context of eye diseases?

Matrix contraction is a process where cells exert force on the extracellular matrix, causing it to shrink. In eye diseases, particularly conditions like macular degeneration, this contraction leads to the formation of epiretinal membranes (ERMs). These ERMs are essentially fibrotic scars that distort the retina, resulting in blurred vision, metamorphopsia, and potentially retinal detachment. The contraction disrupts the delicate architecture of the retina, impairing vision. The Müller cells play a crucial role in this process, as they can transform into myofibroblasts, cells with contractile properties, contributing to ERM contraction.

How do Müller cells contribute to matrix contraction and vision loss?

Müller cells, a type of glial cell in the retina, are central to the process of matrix contraction. They have the ability to transform into myofibroblasts, which are cells with contractile properties. These myofibroblasts within ERMs actively contract, distorting the retinal structure. This contraction leads to vision impairment, including blurred vision and metamorphopsia (distorted images). This disruption of the retina's architecture can also lead to conditions like retinal detachment, further exacerbating vision loss. Therefore, understanding how Müller cells transition and drive contraction is vital for developing effective therapies.

What is the role of FAK and PYK2 in matrix contraction, and how can they be targeted?

FAK (focal adhesion kinase) and PYK2 are members of the FAK family of proteins, identified as key players in matrix contraction. Research has shown that inhibitors of these proteins can reduce matrix contraction in Müller cells. Specifically, the inhibitors PF431396 (FAK/PYK2 dual inhibitor) and PF573228 (FAK inhibitor) were found to be effective. Furthermore, Dasatinib, which inhibits Src-family kinases (SFKs) and Abl kinase, was found to reduce tyrosine phosphorylation of FAK and PYK2. These findings suggest that targeting FAK and PYK2 can prevent or reduce the contraction, potentially mitigating the vision loss associated with related eye conditions.

How does Dasatinib impact the FAK family and what does it tell us about potential treatments?

Dasatinib, a drug that inhibits Src-family kinases and Abl kinase, has a significant impact on the FAK family. Research indicates that Dasatinib reduces the tyrosine phosphorylation of both FAK and PYK2. This reduction suggests that these kinases are downstream targets of Dasatinib's inhibitory action. Furthermore, Dasatinib was found to reduce phosphorylation of Hic-5, a protein involved in cell signaling and focal adhesions, suggesting Hic-5 acts downstream of the FAK family. This understanding opens the door to explore other molecules involved in this pathway for new treatments for eye conditions, and helps to focus research efforts on the FAK family.

What are the future implications of targeting FAK/PYK2 for eye diseases?

Targeting the FAK/PYK2 pathway holds promise for reducing vision loss caused by epiretinal membranes (ERMs) associated with eye diseases. Since several FAK/PYK2 inhibitors are already in development and being tested for cancer treatment, the potential to repurpose or adapt these drugs for ocular conditions offers a new therapeutic avenue. This approach could provide treatments for conditions like macular degeneration and others linked to matrix contraction. Further research is needed to fully realize this potential, but the preliminary findings highlight the potential of FAK/PYK2 inhibitors to become effective treatments in the future, leading to a brighter outlook for vision.