Apr. 16, 2009 Scientists at Schepens Eye Research Institute have found that the growth factor known as TGF-β is essential to the health of blood vessels in the retina and that blocking it can cause retinal dysfunction.
These findings, published in the April 2 issue of PLoS ONE, may have an important impact on the prevention and treatment of diseases such as diabetic retinopathy and macular degeneration.
"These results are significant because they add to our understanding of the molecules that help to maintain blood vessels in a healthy state," says Patricia D'Amore, PhD, senior scientist at Schepens and principal investigator of the study, who adds that this information may be useful in understanding the changes that occur in the retinal microvasculature prior to the development of proliferative diabetic retinopathy.
"Insight into the role of this growth factor may also help clinicians monitor the use of systemic drugs targeting TGF-β, which is elevated in a number of conditions (such as cancer and fibrotic diseases) to limit any vision problems that might occur as a side effects." adds Tony Walshe, PhD, the first author of the study and a Postdoctoral Fellow in the D'Amore's laboratory team.
Capillaries are the smallest blood vessels in the body and the site at which oxygen and nutrients are transferred from the blood to the tissues. A capillary is composed of an endothelial cell, which forms the lining of the small tube, and a pericyte, which wraps around the outside of the tube. Scientists have long believed that communication between these two cell types is necessary to maintain blood vessel structure and function.
According to Walshe, the goal of the PLoS ONE study was to determine if TGF-β plays a role in keeping blood vessels functioning normally. In previous experiments using tissue cultures, the D'Amore laboratory had identified TGF-β as a protein that results from the communication between the two cell types and which they use to maintain the health of the small blood vessels. In the current study, the team wanted to confirm that finding in animals.
To do that, they injected mice with a virus that produces large quantities of soluble endoglin, a protein that would circulate, and then bind to and inhibit TGF-β. When they examined the retinas of treated mice, the team found clear evidence that retinal blood vessels were losing their integrity-blood was not moving efficiently through the smaller vessels into the retina tissue, and fluid was leaking out of the vessels, which does not happen when the vessels are functioning properly. These defects led to the death of ganglion cells (nerve cells in the innermost part of the retina) and a loss of visual function.
According to D'Amore and Walshe, the demonstration of the role played by TGF-β is one more piece of a very complex set of controls that keeps blood vessels and the retina healthy.
Future studies are aimed at exploring what other molecules are involved in maintaining healthy blood vessels and how these relate to the development of microvascular diseases.
Other authors of the study include: Magali Saint-Geniez, Arindel SR Maharaj, Eiichi Sekiyama & Angel E. Maldonado, also of the Schepens Eye Research Institute.
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- Tony E. Walshe, Magali Saint-Geniez, Arindel S. R. Maharaj, Eiichi Sekiyama, Angel E. Maldonado, Patricia A. D'Amore. TGF-β Is Required for Vascular Barrier Function, Endothelial Survival and Homeostasis of the Adult Microvasculature. PLoS ONE, 2009; DOI: 10.1371/journal.pone.0005149
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