RNAi and Age-Related Macular Degeneration

Another application for gene silencing has been wet and dry macular degeneration, which a team of researchers from a range of institutions including the Shiley Eye Institute at the University of California, San Diego, has been studying. The article is HERE.

Age-related macular degeneration is currently the leading cause of blindness among people over the age of 65 and currently affects approximately 10 million people in the U.S. alone. There are two versions of the disease—dry and wet degeneration, but both involve the degradation of the center of the retina called the macula which eventually causes blindness from the center of the eye, outward. Dry macular degeneration is the most common form of the disease, in which cells in the macula slowly die off.
However, a team of clinicians from several institutions including the Shiley Eye Institute and lead by Kang Zhang, a professor of ophthalmology, have recently discovered a genetic link associated with dry macular degeneration. The genetic expression the team identified involves a molecule that assists in the body’s immune response. The molecule, known as tlr3, is triggered by the emergence of RNA that is typically in the form of invading viruses. The molecule’s job is to invade and destroy infected cells in order to prevent further spread of the virus. The problem lies in the over-expression of this molecule which causes it to kill too many cells with the mildest indicator of an intruder, thus increasing the risk for macular degeneration.
Currently, RNAi therapies targeting wet macular degeneration are underway and Zhang’s team is observing them intently. Researchers working on the wet macular degeneration are attempting to isolate a different gene that may cause an overgrowth of blood vessels behind the retina. Since tlr3 is triggered by RNA, Zhang is concerned that the RNAi therapies used to suppress the overgrowth of blood vessels may actually end up triggering the tlr3 molecules in people with a higher genetic variant for it, in which the tlr3 would end up destroying more retinal cells and further degrade vision.
As Zhang’s team strives to develop therapies to treat dry macular degeneration, they also want to explore how the tlr3 molecule reacts in patients with wet macular degeneration and RNAi treatment. Some researchers believe that the molecule will have no effect on RNAi, while others think that the combination of RNAi suppression of blood vessel growth and the cell destruction of tlr3 will cancel each other out and no effect will take place.
In order for the RNAi therapies for macular degeneration to be successfully implemented in our healthcare system, more trials are needed. For example, if patients with a higher propensity for the tlr3 molecule experience adverse effects to the RNAi treatment for wet macular degeneration, then a regulation process must be established to prevent treatment in the wrong people. This could mean screening patients to see if they possess the variant for tlr3 and depending on their results, they would either undergo the RNAi treatment or not, depending on their genotype. This type of additional screening and testing drives up costs considerably and shows how complicated it could be to incorporate RNAi treatments in our future healthcare system due to the wide range of variables.