RetGen

Glaucoma, macular degeneration and the effects of diabetes destroy photoreceptors and other neurons in the retina, the inner lining of the back of the eyeball. Unlike other cells in our bodies, neurons don't naturally regenerate. Once they're damaged, they -- and the eyesight of people with those diseases -- are gone for good.

Early findings by Duke University ophthalmology researcher Dennis Rickman and others indicate that stem cells indeed restore damaged retinas.

"The cells migrate to the area of injury, and in many cases appear to integrate into the tissue and differentiate into those cells," Rickman said.

Researchers took a gene, the pigment epithelium-derived factor (PEDF) gene, and placed it in an adenovirus then injected it directly into the eye. While the virus is unable to replicate, it acts as a vehicle to incorporate the gene into the diseased eye. The gene produces PEDF protein, which inhibits formation of abnormal blood vessels.

"It is encouraging that this method of delivering therapy to the eye can be safely carried out," said Michael Klein, M.D., director of the Macular Degeneration Center at OHSU's Casey Eye Institute and co-principal investigator of the OHSU portion of the trial.

Drusen in patients with AMD contain components known as complement C3 and C5. Ambati's lab has identified that bioactive fragments of these components, known as C3a and C5a, are present in patients whose AMD progresses beyond the early dry stage and into the later wet stage.

Ambati's research concludes that the presence of the C3a and C5a components in drusen are not only markers of AMD that will develop into the late-stage form of the disease, but that they are in fact causal. The presence of these components stimulates the progression of AMD. In the future, patients with early-stage AMD may be screened to determine if these effectors exist in their drusen. If they are present, then these patients could be considered at "high risk" for progression to advanced AMD.

Vascular endothelial growth factor (VEGF) is a substance that promotes angiogenesis - the formation of new blood vessels from pre-existing vessels. In macular degeneration, vessels grow through angiogenesis, destroying the cells that are required for vision. Scientists have long believed that turning off the source of VEGF would lead to halting angiogenesis and disease progression.

Ambati's lab found that while withdrawing VEGF could halt angiogenesis in some areas, it actually encouraged it in others. Upon further investigation Ambati found that this previously undiscovered anti-angiogenic effect of VEGF was mediated via activating VEGFR-1 (VEGF receptor 1) and deactivating VEGFR-2 (VEGF receptor 2). Additionally, his lab found that a compound known as SPARC (secreted protein, acidic and rich in cysteine) could influence and switch the routing of VEGF away from VEGFR-1. Thus, controlling SPARC levels appears to be key to controlling angiogenesis in macular degeneration.