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Undoing the Damage of Glaucoma

3 August 2009 (All day)
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Lambiase et al./PNAS

Reversible? Compared to a healthy eye (left), an eye with glaucoma (right) shows evidence of damage to the optic nerve (white region).

In people suffering from glaucoma, damage to the optic nerve can slowly degrade peripheral vision and, in the worst cases, eventually lead to blindness. But eyedrops containing nerve growth factor (NGF)--a protein that promotes the survival and growth of neurons in the developing brain--appear to prevent nerve damage in rats and restore some vision in three human glaucoma patients, the authors of a new study claim. Not everyone thinks the reported effect is real, however.

For the study, ophthalmologist Alessandro Lambiase of the University of Rome Campus Bio-Medica and colleagues first mimicked glaucoma in rats. The researchers recreated the most common form of the disease, in which increased fluid pressure inside the eye damages nerves, by injecting saline solution into a vein in the eye. They kept the intraocular pressure up for 7 weeks, killing about 40% of the neurons in the retina whose tail-like axons give rise to the optic nerve, which conveys visual information to the brain. However, in rats treated four times daily with NGF-laced eyedrops during the 7-week period, the death of these "retinal ganglion cells" was reduced by about 25%, the team reports online today in the Proceedings of the National Academy of Sciences. (The senior author on the paper is neuroscientist Rita Levi-Montalcini, who shared the 1986 Nobel Prize in physiology or medicine for the discovery of NGF and in April became the first Nobelist to celebrate a 100th birthday.)

Encouraged by these findings, the researchers asked three patients with advanced glaucoma to take the drops four times daily for 3 months. Peripheral vision, one of the main visual functions impaired by glaucoma, improved in two of the patients and got no worse in the third, the researchers report in the same paper. They also report improvements in visual acuity, contrast sensitivity, and in electrophysiological measures of nerve conduction in the visual system in some or all of the patients.

Experts are divided over the findings. "It's very significant if it's real," says Richard Libby, a glaucoma researcher at the University of Rochester in New York state. Other compounds have been shown to have a similar protective effect on rat retinal cells when injected into the eye, Libby says, but the possibility of delivering a neuroprotective drug in eyedrops is "very exciting."

But Harry Quigley, an ophthalmologist and glaucoma researcher at Johns Hopkins University in Baltimore, Maryland, isn't buying any of it. Quigley faults the study's methods, including the lack of human control subjects and the design of the human experiments. Visual field measurements are notoriously susceptible to placebo effects, Quigley says, and because subjects knew they were getting the real treatment, he thinks it's possible the improvements in peripheral vision were due to raised expectations rather than the drug itself.

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