Study Finds Lack of Diffusible VEGF Growth Factor Can Cause Retinal Defects Similar to Dry Macular Degeneration
Discovery may also have impact on the use of new drugs for wet macular degeneration
BOSTON, Nov. 2 /PRNewswire-USNewswire/ -- Scientists at Schepens
Eye Research Institute have found that when the eye is missing a
diffusible form of vascular endothelial growth factor (VEGF), i.e.
one that when secreted can reach other cells at a distance, the
retina shows defects similar to "dry" macular degeneration, also
called geographic atrophy (GA). This finding, published in the
November 3, 2009 print edition of PNAS (Proceedings of the National
Academy of Sciences), not only increases the understanding of the
causes of this blinding disease, but it may also impact the use of
anti-VEGF drugs, such as Lucentis, which are designed to neutralize
VEGF in eyes with "wet" macular degeneration.
"These results are significant for several reasons. We know
little about what causes GA or how to treat it. Our discovery may
be an important piece of the puzzle. It shows that reduced VEGF
from the retinal pigment epithelium (RPE), the bottommost layer of
the retina, to the choriocapillaris (CC) - the small blood vessels
beneath retina-- leads to degeneration of the CC. Therefore, the
continuous blockage of VEGF may contribute to the development of or
a worsening of GA," says Patricia D'Amore, principal investigator
of the study and senior scientist at Schepens.
VEGF is a protein that stimulates the growth of new blood
vessels. The eye produces several different forms of VEGF that
differ in their size and their ability to move away from the
producing cell.
Age-related macular degeneration (AMD) is a disease that
destroys the macula, the central part of the retina responsible for
detailed vision needed for reading, driving and face recognition.
It comes in two types--"wet" and "dry." In wet AMD, a pathological
overproduction of VEGF leads to the development of abnormal blood
vessels, which leak and damage the retina. Wet AMD can be treated
with some success with anti-VEGF drugs that block abnormal blood
vessel growth and leakage. Dry macular degeneration develops less
rapidly, and is related to an accumulation of debris under the
retina that can advance to GA where RPE and underlying vessels are
lost.
Knowing that the RPE in the adult produced VEGF, the Schepens
team hypothesized that in a healthy individual, the RPE produces
forms of VEGF that, when secreted, can move away from the RPE and
reach the underlying CC to support its function and survival. The
CC vessels are extremely important as they supply the
photoreceptors (the light- and color-sensitive cells in the macula)
with oxygen and nutrients necessary for vision.
In the PNAS study, the researchers tested their hypothesis using
a genetic mouse model in which the RPE produced a form of VEGF that
was unable to diffuse. As the mice aged, they began to display an
age-dependent degeneration of both the CC and RPE, culminating with
the death of photoreceptors and vision loss, similar to that
observed in GA.
The next step in the research, according to the first author Dr.
Magali Saint-Geniez, is to determine if this model can be used to
investigate the role of RPE-CC interaction in AMD and to design new
therapies.
Authors of the study include: Magali Saint-Geniez(1)(2), Tomoki
Kurihara(1), Eiichi Sekiyama(1)(2), Angel E. Maldonado(1), and
Patricia A. D'Amore(1),(2),(3).
(1)Schepens Eye Research Institute and the Departments of
(2)Ophthalmology and (3)Pathology Harvard Medical School.
Schepens Eye Research Institute is an affiliate of Harvard
Medical School and the largest eye research institute in the
nation.
Source: Schepens Eye Research Institute
CONTACT: Patti Jacobs of Schepens Eye Research Institute,
+1-617-864-2712, or pjacobs12@comcast.net
Web Site: http://www.schepens.org/
Posted: November 2009
