Focus on Retina
Volume 1, Issue 1
The Retina Center
A CURE FOR MACULAR DEGENERATION - COULD IT BE?
It is the year 2010 and Mrs. Smith goes for a routine eye examination. This 35 year old woman has no visual problems, but she is concerned because her 63 year old mother is now legally blind from AMD. DNA analysis from blood specimens reveals that Mrs. Smith and her mother both have a mutation in a gene on the long arm of chromosome 11, a known cause of macular degeneration. Individuals with this type of AMD (type 6) have a 90% risk for severe vision loss by age 65. The latest studies of this mutation in transgenic mice suggest that a diet high in vitamin B6 delays the onset and reduces the severity of this subtype of AMD.
UPDATE- Mrs. Smith takes vitamin B6 in therapeutic doses for the rest of her life. She develops the first signs of AMD at age 80, and by the time she dies at age 88 she has had only minimal difficulties with her vision.
THE FACTS - HOW FAR HAVE WE GOTTEN WITH THIS?
The above example is more than just a dream. Mutations in the ABCR gene were first found to cause Stargardt’s disease, an autosomal recessive macular dystrophy characterized by juvenile-onset macular degeneration. Researchers speculated that a less severe mutation in the same gene might cause a later onset macular degeneration (i.e. AMD). When they examined a large number of individuals with AMD, they found 13 different alterations in the ABCR gene which were found significantly more frequently in AMD patients than in controls. 16% of AMD patients had these "AMD-associated alterations." (Science 1997;277:1805). The study’s authors concluded that mutations in the ABCR gene play a role in a subset of patients with AMD. We at The Retina Center are skeptical of this conclusion based on some problems with the statistical methods used (attend our upcoming journal club to discuss this paper in more detail). However, it is clear that numerous AMD-causing genes remain undiscovered.
The power of the genetic approach to AMD has led us to modify the way we approach our patients. In order to isolate the genetic defects that cause AMD, families with large numbers of affected individuals are most helpful. Since the parents of individuals with AMD are usually deceased, and their children are typically too young to be affected, the family history should concentrate on living siblings. Of course, many individuals with AMD are asymptomatic and unaware that they are affected. Thus, a family with numerous living siblings is often worthy of study even if only one individual is known to be affected. While it typically requires 12 or more affected individuals in a single family to locate a gene, by combining several families, even small pedigrees can make a big difference.
Patients with families spread out over a large geographic area can be studied with the help of colleagues. The blood tests needed to support the studies are all done in an affiliated laboratory at The University of Iowa where Dr. Goldman did his fellowship training.
MEDICATIONS FOR AMD - WHAT’S WRONG WITH THE VITAMIN STUDIES?
Since AMD is likely to be a number of genetically distinct diseases, is there any reason to assume that they all will benefit from the same treatment? Probably not. Nevertheless, studies investigating potential treatments often lump all patients with AMD together assuming they have the same disease. This approach risks overlooking the benefit that a particular treatment has for a given subset of AMD patients. For example, let’s use the fictitious example described above and assume that patients with AMD due to a particular mutation benefit dramatically from vitamin B6 (or zinc, or selenium, or whatever). If a study randomly lumps 10 of these AMD patients together with 90 others with different mutations (which don’t benefit from B6), the treatment benefit might be diluted out. Researchers would then incorrectly conclude that B6 is not beneficial for patients with AMD when in fact it might greatly benefit a small subgroup of individuals. This phenomenon may explain why vitamins and minerals have not yet been shown to be helpful for AMD (and we do not currently recommend them). Fortunately, the identification and study of genetically homogeneous subgroups is just around the corner. This approach will be much more likely to identify effective treatments for this frustrating and increasingly prevalent disease.
WANTED: BLOOD
Through an affiliation with the University of Iowa Molecular Ophthalmology Laboratory, The Retina Center offers genetic screening for families with heritable retinal disease (including AMD). Valuable blood testing is done at no charge to your patients.