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June 29, 2009
Targeting Age-Related Macular Degeneration
Researchers have identified a key molecular player in a type of age-related macular degeneration (AMD). The discovery may lead to better methods of early detection and treatment for this leading cause of blindness.
AMD gradually destroys sharp, central vision as a person ages. You need central vision to see objects clearly and for common tasks such as reading and driving. AMD comes in 2 forms: dry and wet. Although the dry form is much more common, the wet form leads to significantly more vision loss.
Wet AMD is caused by abnormal blood vessels growing in the layer of the eye named the choroid, which lies beneath the light-sensitive retina. This blood vessel growth is known as choroidal neovascularization (CNV). The new blood vessels tend to be very fragile and often leak blood and fluid. As they grow under the macula in the center of the retina, they raise the macula and damage it, eventually destroying your ability to see fine detail. An early symptom of wet AMD is that straight lines appear wavy. No current treatments can cure wet AMD, but treatment can help slow vision loss and, in some cases, improve sight.
A team of researchers led by Dr. Jayakrishna Ambati at the University of Kentucky searched for molecular markers of CNV. Supported by NIH鈥檚 最新麻豆视频 Eye Institute (NEI) and several other sources, they examined specimens of CNV tissue taken from patients with wet AMD.
In the June 14, 2009, online edition of Nature, the team reported finding a protein called CCR3 on the surface of blood vessels in the tissue samples. CCR3, best known for its role in inflammation, isn鈥檛 normally found on blood vessels. Using cultured choroid cells, the researchers found that blocking CCR3 prevented choroid cells from forming tubes, an important step in forming blood vessels.
The scientists then looked at CNV that they induced in mice using a laser. When they blocked CCR3 in the eye, the researchers found that CNV was suppressed. They next compared this approach with a current wet AMD treatment. Blocking CCR3 proved more effective in the mice, reducing CNV by about 68%, as opposed to 57% for the current therapy. The CCR3 treatment also proved less toxic to the mouse retinas.
Another problem with current methods is that researchers can鈥檛 detect CNV in the choroid before it has advanced into the retina. Therefore, the scientists studied the ability of small antibody fragments that bind to CCR3 to detect CNV before it appears in the retina. They attached the antibodies to tiny nanocrystals called quantum dots and injected them into mice. Using this CCR3 tracking method, they were able to spot CNV in the choroid that current methods couldn鈥檛 detect until it appeared in the retina.
鈥淲ith CCR3, we have for the first time found a unique molecular signature for the disease,鈥 Ambati says. Eventually, CCR3 might prove a safe and effective target to detect and treat CNV early, before vision is lost.
鈥攂y Harrison Wein, Ph.D.