In a recent study, Moran Eye Center's Dr. Mary Elizabeth Hartnett looks for a way to fix or maintain the retinal pigment epithelial (RPE) barrier. And she found it in the protein RAP1A. Her research, "Retinal pigment epithelial cell expression of active Rap1a by scAAV2 inhibits choroidal neovascularization," was published in Molecular Therapy Methods & Clinical Development, August 24, 2016.
Why is this promising research important? Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In neovasular (wet) AMD, new blood vessels grow under the retina. These blood vessels then leak, making the RPE barrier weak, allowing abnormal cells to migrate across the RPE into the retina, compromising vision.
Since blood vessels grow in response to vascular endothelial growth factor (VEGF), one current treatment for vascular AMD is to block VEGF with anti-VEGF injections. This therapy is successful in about 40 percent of patients, but is far from perfect. "Some problems with anti-VEGF injections are that VEGF can also be beneficial to specialized retinal cells," says Hartnett. "And, if you get to the point where you don't need anti-VEGF anymore, continuing to remove VEGF, theoretically, could harm the eye and increase the likelihood of advanced dry forms of AMD."
In a cell, RAP1A turns on and off as needed to control the retinal pigment epithelial cell's ability to have strong barriers. What she discovered in this study is that "RAP1A, when activated," says Hartnett, "prevented invading blood vessels as well as the anti-VEGF treatment did in RAP1A-deficient mice."
So as an alternative to anti-VEGF injection, being able to inject an activated RAP1A may also benefit not only AMD, but other conditions associated with a weak RPE barrier. "This is new experimental research that may have a role in precision medicine, in which patients with deficiencies in the ability to activate RAP1A may benefit," says Hartnett. "As we learn more about people with certain genetic makeups that cause them to resist current therapies, novel therapies such as active RAP1A may provide a therapy."