Scientists Discover a Role for the Growth Factor TGF-beta in Maintaining Health of...

Scientists Discover a Role for the Growth Factor TGF-beta in Maintaining
Health of Retinal Blood Vessels

BOSTON, April 7 /PRNewswire-USNewswire/ -- Scientists at Schepens Eye Research
Institute have found that the growth factor known as TGF-beta 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-beta, 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-beta plays a role in keeping blood vessels functioning normally. In
previous experiments using tissue cultures, the D'Amore laboratory had
identified TGF-beta 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-beta. 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-beta 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.

To review the article, go to:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005149

Schepens Eye Research institute is an affiliate of Harvard Medical School and
the largest independent eye research institute in the nation. For additional
information about the Institute, go to: www.schepens.harvard.edu.

SOURCE Schepens Eye Research Institute

Patti Jacobs of Schepens Eye Research Institute, +1-617-864-2712,
Pjacobs12@comcast.net