New Gene Linked to Macular Degeneration
Variants of SerpinG1 Gene May Protect Against Ophthalmic Disease
Oct 26, 2008
Age-related macular degeneration, also called ARMD, is the leading cause of blindness in people aged 65 and over, in Western countries. There are approximately 30 million people worldwide affected by macular degeneration.
In some severe cases, the disease can cause as much as 90% loss of central vision, although, most patients retain a certain amount of peripheral vision even after the disease sets in. Because of this, numerous daily activities, which require good central vision, such as driving, reading and carrying out most professional responsibilities are hindered and become difficult to carry out. Other less demanding activities, such casual walking and many domestic activities, which can rely on peripheral vision can be, for the most part, continued without much trouble.
Macula and Retina
The macula is an oval yellow spot on the retina, near the center of the posterior pole in the human eye. It is in this spot that visual acuity is maximal. Behind the retina is a membrane called the choroids, which contains the necessary blood vessels that supply blood to the retina. In the most severe form of age-related macular degeneration, these blood vessels grow excessively to the extent that causes the retina to become detached from the eye.
Typically, the disease can be treated by helping the retina re-attach, either by laser coagulation or by special anti-angiogenic drugs that target proteins regulating blood vessel growth. These treatments, however, do not always restore to a full extent, the loss of vision suffered.
Variant Forms of SerpinG1 Help Protect Against ARMD
In October 6th, 2008, Dr Sarah Ennis and Dr Andrew Lotery of the Southampton General Hospital (Southampton, UK) in collaboration with Prof Edwin Stone of the Howard Hughes Medical Institute (Chevy Chase, USA), reported the role of a variant of SerpinG1 gene, the “rs2511989” (a Single Nucleotide Polymorphism) in age-related macular degeneration of two independent populations a group of 958 patients from UK, and then confirmed in a group of 500 American patients.
The study ”Association between the SerpinG1 gene and age-related macular degeneration: a two-stage case-control study” has been published in the medical journal The Lancet (Oct 2008). The researchers found that the rs2511989A variant gene occurred less frequently (or was absent) in patients affected by the disease, than in healthy patients. In other words, this form of the SerpinG1 gene had some protective effect against the disease and therefore, people carrying such a gene had half the risk of developing age-related macular degeneration.
Biological Relevance
The SerpinG1 gene produces the SerpinG1 protein, a member of a group of enzymes called proteases, which digest other proteins. The SerpinG1 enzyme is already known as a major player of an important biologic pathway called the Complement system. The Complement system is a component of the innate immune system.
Other genes of the Complement system, such as CHF (Complement Factor H) and C3 (Complement 3) have also been involved in age-related macular degeneration. Without knowing the precise biological mechanisms involved, the new addition of the SerpinG1 gene to the list of genes associated with ARMD, highlights the importance of proper regulation of these genes in the maintenance of macular function and it also inspires a new therapeutic avenue to target age-related macular degeneration.
