The Conundrum of Research
One day, research in molecular genetics will open many doors in terms of the diagnosis and treatment of eye diseases such as glaucoma and age-related macular degeneration. Overall, however, we’re not there yet. Challenges include the following:
Macular Degeneration and Glaucoma: We have a gene, but no test.
For many years, ophthalmologists have known that age-related macular degeneration tends to run in certain families. The strongest evidence yet of a genetic component to macular degeneration came last spring, when four independent teams of researchers came up with the same finding: People who inherit a particular form of one gene have a 3–7 fold greater risk of developing age-related macular degeneration.
The researchers implicated one of several variants of the gene that encodes a protein called complement factor H (CFH). Normally, CFH helps regulate inflammation in part of the immune system that attacks diseased and damaged cells. This version of the gene may fail to put the brakes on inflammatory proteins such as C-reactive protein. And that possibility is an intriguing one, as C-reactive protein, which is a systemic marker of inflammation in the body, plays a role in a number of diseases, including age-related macular degeneration and cardiovascular disease. All told, this variant of the CFH gene might be responsible for 43–50% of age-related macular degeneration risk, the reports suggested.
However, while these studies confirm that there is a strong genetic component to age-related macular degeneration, and they give researchers a new area to focus on, ophthalmologists and their patients— particularly those with a family history of age-related macular degeneration —are a long way from having a practical blood test to screen for macular degeneration. Eventually, when a blood test is developed, it’s possible that it could be used in conjunction with new imaging technologies to detect the earliest signs of age-related macular degeneration.
One additional caveat: As with many diseases, environmental factors still play a significant role in age-related macular degeneration. In a separate study of 840 male twins published last year, genetic factors were estimated to explain 46–71% of the variation in the severity of the macular degeneration, with environmental factors such as cigarette smoking and obesity accounting for the remaining 29–54%.
Macular Degeneration and Glaucoma: We have tests, but no new treatment.
Screening tests are available for two of the genes that cause primary open-angle glaucoma. But many glaucoma specialists are reluctant to order them because they have no gene-specific therapy to offer the average person with glaucoma other than additional “watchful waiting.”
The tests target two of the genes that cause open-angle glaucoma: myocilin and optineurin. Mutations in myocilin (also called TIGR or GLC1A) cause almost all cases of familial juvenile onset open-angle glaucoma, and 3–5% of cases that occur in adults. Mutations in optineurin (also called OPTN or GLC1E) cause less than 1% of adult-onset cases of open-angle glaucoma.
But while the myocilin and optineurin tests will indicate whether you do or don’t have the gene mutation, they can’t predict whether you will go on to develop glaucoma. And again, if the gene variant is detected, that diagnosis won’t radically change your life— there is no different or specific treatment to offer you. The only rationale for testing might come in families with a very strong history of juvenile-onset glaucoma. In those cases, if a child or adolescent with juvenile-onset glaucoma is found to have a mutation in the myocilin gene, it might be appropriate to test other children in the family to see if they have the same mutation. If that proves to be the case, then those children should be rigorously monitored for any early signs of juvenile-onset glaucoma development.
