Feb. 2, 2008 Erythropoietin has so far been known to doctors as a hormone that boosts red-blood-cell production. Now, a mouse study led by Lois Smith, MD, PhD, an ophthalmologist at Children's Hospital Boston, shows it also keeps blood vessels alive and growing in the eye. The findings not only add a new function to the hormone, but also give doctors a reason to pause before prescribing it to patients with diseases affected by abnormal blood-vessel growth, such as retinopathy and cancer.
The study also found that whether the hormone is a risk or benefit depends on the timing of administration.
Smith and first author of the study* Jing Chen, PhD, worked in mice with retinopathy, an eye disease that begins when healthy blood vessels nourishing the retina die. Numerous vessels then grow in, but they are deformed. Ultimately, the deformed vessels may pull the retina off the back of the eye, causing blindness.
The researchers measured erythropoietin produced in the retina as the disease progressed. Production was 3 to 10 times below normal during early-stage retinopathy, when healthy blood vessels died, and 12 to 33 times above normal during late-stage retinopathy, when deformed blood vessels grew into the retina. The researchers concluded that erythropoietin helps blood vessels survive and grow in the retina, with effects that may be healthy or harmful.
Next, the team examined whether giving erythropoietin could treat retinopathy. They injected erythropoietin into the bloodstream either early, as the mice lost healthy blood vessels, or later, when deformed blood vessels began to invade--then compared them with untreated mice.
Boosting erythropoietin early slowed the disease. The mice lost half as many healthy blood vessels, causing about 30 percent fewer deformed vessels to grow in. Raising erythropoietin levels later, when deformed blood vessels were present, appeared to accelerate the disease--slightly more deformed blood vessels grew in.
If similar effects are found in humans, and its use is properly timed, then giving erythropoietin early could slow loss of healthy blood vessels in retinopathy, says Smith. "Right now, there is very little out there to treat blood vessel loss in patients with retinopathy. However, further studies on the restoration of normal levels of erythropoietin are needed to translate these results to patients."
In other diseases, like cancer, in which doctors need to slow blood vessel growth, the hormone could be blocked, although clinical trials would need to confirm this idea, she adds.
But given at the wrong time, erythropoietin may make blood vessels grow in an unhealthy way, says Smith. For example, because it boosts red blood cells, erythropoietin is often prescribed to premature babies and diabetic adults for anemia. Some of these patients also have retinopathy. Giving the hormone at the wrong time might help anemia, but worsen the eye disease.
"We're not saying, 'don't do it.' We're saying, 'think about it,'" says Smith. "Physicians should look at the state of the eye before giving erythropoietin to patients with retinopathy. They should consider not giving it to patients with full-blown retinopathy, in which abnormal vessels are present, because our work suggests it may accelerate the disease. However, if a patient is early on in the disease, then our work suggests erythropoietin may be beneficial."
Cancer patients, who often take erythropoietin for anemia, face a similar potential risk, says Smith. "Since erythropoietin has the potential to make blood vessels in tumors grow, it could make tumors worse, although a clinical trial is required to know if this is true in humans."
Overall, Smith says her mouse studies are a reason for doctors to think and researchers to investigate, not for patients to panic.
*This research was published in the February issue of the Journal of Clinical Investigation (online January 24).
The research was funded by the V. Kann Rasmussen Foundation, the NIH, Children's Hospital Boston, the Juvenile Diabetes Foundation, and the Research to Prevent Blindness organization.
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