Study Finds Lack of Diffusible VEGF Growth Factor Can Cause Retinal Defects Similar to Dry Macular Degeneration

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

Patti Jacobs of Schepens Eye Research Institute, +1-617-864-2712, or
pjacobs12@comcast.net