by Judy Prevost
March 4, 2000
In the past few years, researchers have leaned a great deal about genetics and Macular Degeneration. In fact, this might be one of the most important areas of research that will result in a better understanding of all of the sub groups of MD, leading eventually to a cure for the disease.
Each one of us came into this world with genes inherited from our parents, and sometimes one or more of these genes is defective. Scientists have found that family members of patients with MD are more than twice as likely to develop the disease, compared to those without such a family history. With this newfound evidence of an underlying genetic predisposition, medical researchers are now examining genes that may be associated with MD.
It is now understood that as many as 20-40 different MD-related gene defects will be discovered. It is difficult to fully understand or identify accurately these genes, as each gene has numerous defects or mutations.
Progress is being made, and in 1997 scientists isolated the gene for autosomal recessive Stargardt's disease (also known as fundus flavimaculatus). Stargardt's disease, the most common form of MD, accounts for approximately 7% of all inherited retinal degenerative diseases. Studies indicate that the ABCR gene produces a protein which transports another substance to and from photoreceptor cells in the retina. Mutations in the ABCR gene, which cause Stargardt's disease, produce a dysfunctional protein that cannot perform its transport function. As a result, photoreceptor cells degenerate, and vision loss occurs. The discovery of this gene allows researchers to better understand the precise function of the gene and to identify what it is that the gene transports.
As recently as two years ago, researchers mapped a gene causing an autosomal dominant form of age related macular degeneration to chromosome 1. Gene mapping is the process of identifying which of the 23 paired chromosomes contains a gene with disease causing mutations. In the same time period, researchers reported the discovery of mutations in a gene which causes Best disease. This disease (also known as vitelliform macular dystrophy) is an autosomal dominant form of MD, which is usually diagnosed during childhood or adolescence. Scientists can now study the protein it produces to better understand its function in the retina.
For the future, gene therapy represents the best treatment for retinal degenerative diseases. By delivering healthy genes to cells affected by genetic mutations, researchers may be able to correct most genetic conditions causing vision loss. Every retinal cell requires that a host of genes produce very specialized proteins that are essential to the cell's function. A disease-causing mutation in most genes involved in the retina will alter the production of a normal, functioning protein and lead to retinal degeneration.
Gene therapy is the introduction of a healthy functioning gene into cells so that the cells can then function properly. In scientific language, gene delivery systems are called vectors. Most vectors are derived from viruses, which are very effective at infiltrating the nucleus of a cell where genes reside. Viruses also contain harmful elements that bring on immune responses. Researchers are presently working to genetically modify viruses to hopefully eliminate their harmful qualities without compromising their delivery capabilities. For example, vaccines that prevent a variety of infectious diseases like small pox and measles are composed of modified viruses. If gene therapy is to succeed, progress must be made for developing safer and more effective viruses.
Gene studies are presently underway, and candidates are being studied to examine the genetic basis of MD. Scientists first try to identify genes which are likely to contain mutations that cause disease. In the case of MD, the genes in the retina, or specifically in the macula, are the ones most closely observed. Once identified, doctors then screen patient blood samples to look for disease-causing mutations. This study will then eventually reveal which genes accompany this disease.
An understanding of the genetic basis of MD will help tremendously in the fight against the disease. With this newly acquired knowledge, family members at risk could be identified through genetic testing. Researchers and scientists could then develop pharmaceutical and gene based therapies that could result in addressing the underlying genetic dysfunction that causes severe vision loss.
For further information about inheritance, read the following pages on the MD Support web site:
Types of Juvenile Macular
Degeneration
Stargardt's Disease