According to a new study by MIT researchers a DNA repair system that normally protects cells from damage can cause retinal degeneration and blindness when overstimulated. The research team found that relatively low-level exposure to an environmental toxic agent provoked very active DNA repair that led to surprisingly high rates of retinal degeneration in mice -- much higher than in mice lacking the same DNA repair pathway. The work raises the possibility of developing treatments for retinal degeneration by blocking a particular DNA repair pathway.

Leona Samson, co-director of MIT's Center for Environmental Health Sciences, professor of biology and biological engineering, and senior author of a paper on the work appearing online in the Proceedings of the National Academy of Sciences this week stated: too much DNA repair is not a good thing and could actually be a bad thing, The scientists studied a pathway involving an enzyme called Aag. The enzyme has a human analogue called AAG that may play a role in retinitis pigmentosa (RP), a group of genetic eye disorders that lead to blindness.

Under normal levels of exposure the system functions effectively. However, but if mice were exposed to a higher  level of toxic agent, the system backfired. Aag cuts out so many bases that the rest of the DNA repair system cannot keep up, leading to death of the rod and cone cells that make up the retina. This malfunction in the DNA repair pathway occurs only in certain body tissues, including the retina, and only in mice with normal Aag levels. Mice lacking Aag do not exhibit retinal degeneration, while mice with high Aag levels had even higher levels of retinal degeneration.

 By Vasil Sidorov on March 8, 2009 after MIT's Center for Environmental Health Sciences