Findings: Advanced forms of dry age-related macular degeneration (AMD), called geographic atrophy, can lead to severe vision loss or blindness. Currently, there are no effective treatments for dry AMD (unlike wet AMD, which has several treatment options).

Over a tenth of the human genome is “junk” DNA that makes a product called Alu RNA. In healthy people, a protein called Dicer1 chops up these Alu RNAs. This research team found that people with this advanced form of dry AMD have lower levels of Dicer1 in particular retina cells called retinal pigment epithelium (RPE). There is a buildup of the Alu RNA that then kills these cells, leading to blindness. A team of researchers, including BrightFocus-funded Dr. Judit Baffi, has identified that the Alu RNA buildup triggers the activation of another protein that then leads to RPE cell death. The scientists prevented this protein, called ERK1/2, from killing the RPE cells in mice by using a compound that specifically blocked its activation.

Significance: This research is the continuation of pivotal BrightFocus-funded discoveries that were published in 2011 and in early 2012 (see links to those descriptions below). In this latest breakthrough, the team identified that ERK1/2 protein is the “contract killer” of RPE cells in mice, “hired” by the buildup of Alu RNA. If further testing is successful, in the future, drugs could be designed to target ERK1/2 as a treatment option for this blinding form of dry AMD.

BrightFocus funded Dr. Judit Baffi, was a pivotal member of this research team. Senior author on this paper, Dr. Jayakrishna Ambati (http://www.brightfocus.org/research/grants/migrated/adenoassociated-viral-gene-therapy-in.html) and (http://www.brightfocus.org/research/grants/migrated/the-role-of-sparc-in-macular-propensit.html) is a former BrightFocus grantee.

• Original Research Article
• Eurekalert/University of Kentucky press release
• This is the continuation of research on important discoveries reported by Drs. Baffi, Ambati, and colleagues in the journal, Nature, on February 6, 2011 and reported in the journal, Cell, on May 2, 2012.