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Potential Topical Treatment in the Future for Macular Degeneration
Researchers from the Tufts University School of Medicine have found a possible topical treatment for age-related macular degeneration (AMD) by applying a molecule called PPADS to the eye in the form of eye drops.
AMD is a chronic eye disease marked by blindness in the center of one’s field of vision. According to Associate Professor of Ophthalmology Rajendra Kumar-Singh, AMD is probably the most common cause of blindness in the elderly, with as many as seven million individuals in the United States at risk.
Kerstin Birke, a postdoctoral scholar in the Department of Ophthalmology, explained that there is a dry form and a wet form of AMD. Dry macular degeneration is characterized by the degeneration of the macula, the region of greatest visual acuity, located at the center of the retina. Wet AMD is caused when blood vessels growing under the retina begin leaking blood and fluid.
While 90 percent of patients suffer from the dry form, the only treatment currently available is solely for the more serious wet form, Birke said. This involves going to the ophthalmologist about every six weeks to have drugs injected directly into the eye — a very inconvenient process for both patient and doctor with significant side effects.
Jay Duker, professor and chair of the Department of Ophthalmology at Tufts School of Medicine, explained that the current treatment forces those with AMD to become dependent on their doctors.
“Patients are tied to their retina specialists for the rest of their lives to have injections performed every month or two, or they’re going to lose vision,” he said.
Kumar-Singh was excited to find the topical solution, as the treatment has the potential to treat both the wet and dry forms of AMD.
“In the vast majority of patients, the wet form is preceded by the dry form, and hence we believe that if we can block the progression of the dry form of the disease, we can treat both the dry form and the progression to the wet form,” Kumar-Singh said.
The research team used mice to test its treatment, Birke explained. Since mice do not naturally experience macular degeneration, the research team had to induce damage to their retinas using a laser. This led to the formation of new blood vessels and mimicked the wet form of AMD, as well as some features of the dry form, like activation of the immune system complement. Such activation resulted in the formation of membrane attack complex (MAC) on cells, which punched holes in the cells, Birke said. The researchers then administered PPADS eye drops on the mice to see if they could reach the affected area by topical application.
“PPADS acted on the area damaged by the laser, and we could see approximately 50 percent reduction in blood vessel formation,” she said. “We also saw a reduction in the formation of the membrane attack complex that is believed to play a very significant role in the dry form of AMD, so it seems that this molecule could act on both forms of AMD.”
Birke noted that there are still problems the research team must face before PPADS can proceed to clinical trials.
“It’s a very broad molecule, and it acts on many receptors,” she said. “The ideal molecule would be an analog of PPADS which only acts on the pathway that is activated through the disease process.”
Kumar-Singh added that this treatment will take many years to perfect and test for safety.
“We don’t know about the relevant similarities and differences between mouse eyes and human eyes, and that’s what concerns me the most,” he said. “Even though the mouse is a very good model, there are differences.”
However, researchers like Duker are still hopeful.
“If [PPADS] works, we will be able to free patients up from having to come into the office on such a regular basis and having this invasive procedure performed,” Duker said. “They’ll be able to treat their macular degeneration at home by putting drops in their eyes.”
Kumar-Singh believes the research may prove to be very important for the future of elderly care.
“It is my opinion that if all of this works out well, it will have a very large impact on AMD,” he said. “I think it would be, for want of a better word, a game changer.”
Source: www.tuftsdaily.com, October 24, 2013