Eyes on Epo
Authors: Davenport R. John 
Published: August 2003

A wonder drug for the blood now shows promise in protecting vision. New work suggests that erythropoietin (Epo), a natural hormone used to treat anemia in cancer and AIDS patients and to illicitly boost performance of endurance athletes, helps prevent deterioration of rodent retinas. The work illuminates a molecular pathway that protects eye cells and offers promise for treating a disease that steals vision in older people.
By age 65, one in four Americans suffers from macular degeneration (MD), an untreatable disease in which light-sensitive cells in the retina die. The affliction disrupts vision in the eye's center, making reading and detail work difficult or impossible. MD's triggers remain fuzzy, but epidemiological studies suggest that smoking, poor diet, and extended exposure to sunlight are likely culprits. Scientists posit that MD results when retinal photoreceptor cells commit suicide through a process known as apoptosis. Epo blocks apoptosis in blood cells, and recent work suggests that the drug rescues neurons as well. Building on that knowledge, cell biologist Christian Grimm of University Hospital in Zürich, Switzerland, and colleagues explored whether Epo can sustain retinal cells in rodents.

Although long-term oxygen starvation fosters retinal cell degeneration, brief oxygen deprivation prevents intense light from damaging mouse photoreceptor cells. To investigate whether Epo contributes to this protective effect, Grimm and colleagues studied two groups of mice that had been exposed to either normal or low oxygen concentrations for 6 hours. The scientists then subjected the animals to intense light for 2 hours, dilating their pupils and using toys and food to encourage the rodents to keep their eyes open. After this treatment, the team measured the amount of Epo messenger RNA (mRNA) produced by photoreceptor cells. Animals that breathed low oxygen carried nearly 10 times more Epo mRNA in their retinas than did controls. Further experiments identified what cranks up Epo mRNA production: The low-oxygen treatment prevents cells from destroying a protein called HIF-1, which activates the
Epo
gene. With more HIF-1, Epo quantities rise.

Additional studies bolster the connection between Epo and retinal cell maintenance. The team injected the hormone into the abdomens of mice raised under normal oxygen concentrations and exposed them to intense light. The treated rodents lost fewer photoreceptor cells than did untreated ones. Together, the data suggest that elevated amounts of Epo preserve photoreceptor cells, at least in mice. Epo's utility in human eye diseases awaits further proof, says lead author Grimm, and the hormone can thicken blood and hinder circulation. But companies are already seeking Epo derivatives that selectively target neurons and leave blood cells untouched, he says. Such compounds might slow MD's progression while minimizing side effects.
That Epo protects mice from light damage is exciting, says retinal degeneration researcher Michael Danciger of Loyola Marymount University in Los Angeles, but the experiment might not mimic the degeneration that occurs in age-related MD. Follow-up experiments should probe whether Epo protects eyes in a mouse version of MD, he says. That line of inquiry could help bring Epo's vision-protecting potential into focus.
--R. John Davenport; suggested by Amir Sadighi Akha

C. Grimm, A. Wenzel, M. Groszer, H. Mayser, M. Seeliger, M. Samardzija, C. Bauer, M. Gassmann, C. E. Remé, HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration.
Nat. Med
.
8
, 718-724 (2002).
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