Download As Rods Go, So Go the Cones

As Rods Go, So Go the Cones
By Michael Price
ScienceNOW Daily News
8 December 2008
Rod cells in our eyes help us see in dim light. They also ensure that the
cones, the other light-sensitive cells we depend on for vision, get enough
food, a new study reveals. The findings may shed light on a common cause of
blindness.
Approximately 100,000 people in the United States have retinitis pigmentosa,
an incurable inherited retinal disease that leads to blindness. More than 40
genes can contribute to the disease, often by damaging important proteins in
retinal cells. The disease's initial symptom, night-vision loss, appears when
rods start dying off. This attrition usually begins in childhood, and though it's
inconvenient, most people get by with their cones--the photoreceptive cells
that work in bright light. But by the time affected people reach adulthood, the
cones begin dying, too, ultimately resulting in total blindness. This has
confounded scientists, because the faulty genes aren't active in the cones,
only in the rods.
To crack this mystery, biologist Constance Cepko of Harvard University and
her colleague Claudio Punzo, a postdoctoral researcher, first evaluated
previous theories. Some researchers thought that when the rods died, they
produced a toxin that killed the cones. Others hypothesized that because rods
use lots of oxygen in the retina, their death might leave behind a large amount
of oxygen that overloads and damages the remaining cones. But neither of
these seemed to fit the pattern, Cepko says, so he and Punzo decided to look
for a new explanation.
The researchers measured gene activity in four different strains of mice with
defective rod cells. They discovered more than 200 genes that are switched
on at about the same time the cones started dying, many of them related to
cell metabolism.
"That was our first clue that perhaps the cells weren't getting enough
nutrients," Cepko says. Several of these genes were tied to a protein known
as the mammalian target of rapamycin, or mTOR, which lets the cell know
whether it has enough nutrients--especially glucose. But if starvation lasts
long enough, mTOR directs the cell to digest itself. That's exactly what the
cones were doing.
To determine whether a glucose drop-off was killing the cones, the
researchers abdominally injected some of the mice with insulin to increase
their glucose levels. The shots did cause the cones to hang on a little longer,
but they nonetheless died a few weeks later.
Cepko and Punzo think the cones might starve because of the retina's
crumbling architecture. A thin layer of cells, known as the retinal pigment
epithelium (RPE), covers the rods and cones like a circus tent and delivers
their nutrients. Rods significantly outnumber cones in the retina, so when they
die, most of the RPEs' "tent poles" die with them. The tent collapses, the
cones lose their nutrient connection, and they slowly starve. The study is
published online this week in Nature Neuroscience.
"I think it's very exciting," says Rafael Caruso, an ophthalmologist with the
U.S. National Eye Institute in Bethesda, Maryland. "It's a new approach to the
problem." Caruso says that the researchers "make a pretty persuasive case
for their conclusions," especially because the same mutations in the tested
mice are also found in humans.
Unfortunately, both Cepko and Caruso agree that the finding does little for
researchers looking for treatments. But it does suggest a new framework for
thinking about the problem. By exploring different ways to get nutrients into
the cones, Cepko says, researchers might one day be able to help people
with retinitis pigmentosa keep their daytime vision for a longer period of time.