Andreia Goncalves, Ph.D., with David Antonetti, Ph.D., study immunostained retina
A New Regulator of Retinal Angiogenesis Discovered Blood vessel growth (angiogenesis) has been shown to be an important factor in diseases from diabetes to cancer. Under-
Heme is recognized primarily as a component of hemoglo-
standing how the process is regulated, especially in the brain
bin in red blood cells that carry oxygen. However, heme also
and retina, may yield new treatments for many eye and other
contributes to a wide range of functions in other cells,
Funded by a Stein Innovation Award from Research to Prevent Blindness (RPB), David Antonetti, Ph.D., is advancing a novel hypothesis that sheds new and important light on neural-angiogenesis. When looking for genes uniquely expressed in the blood vessels of
including the regulation of gene expression and
“
the retina and brain, Dr. Antonetti and post-doctoral research fellow Andreia Goncalves, Ph.D., were in-
the production of energy by mitochondria. Studies performed by Dr. Goncalves revealed that by reducing heme content in retinal endothelial cells, the blood
THESE AND ADDITIONAL STUDIES
vessel cells grew markedly faster.
PROVIDE STRONG EVIDENCE THAT A
By adding heme back to the cells, this process was reversed.
VARIATION IN HEME CONTENT IN RETINAL
“These and additional stud-
AND BRAIN ENDOTHELIAL CELLS ACTS LIKE
“
central nervous system diseases.
ies provide strong evidence that a variation in heme content in retinal
A RHEOSTAT, SIGNALING BLOOD VESSELS
trigued to find FLVCR2. A mutated
WHETHER, HOW, AND HOW MUCH TO GROW.
form of FLVCR2 is known to drive
— David Antonetti, Ph.D.
the development of Fowler Syndrome, a rare and deadly prenatal disorder that halts the growth of blood vessels but only those in the brain and the retina, with no impact on angiogenesis elsewhere in the embryo.
Since the FLCVR2 gene codes for a transporter of heme,
and brain endothelial cells acts like a rheostat,” explains Antonetti, “signaling blood vessels whether, how, and how much to grow.” Further studies are planned in the Antonetti lab to explore the link between
FLVCR2, endothelial heme content and brain/
retinal angiogenesis. This has the potential to
profoundly impact the identification and development of new
Drs. Antonetti and Goncalves employed various gene editing
therapeutic targets for a number of blinding eye diseases and
and analysis tools in cell culture and animal models to explore
neurological disorders.
a novel hypothesis: that heme contributes to the control of blood 20
vessel growth.