In a recent article in the New England Journal of Medicine, researchers proposed that men with certain genetic mutations might be at increased risk of developing macular degeneration, an eye disease which affects the macula, the area of the retina responsible for sharp, central vision.
The team from the Brigham and Women’s Hospital in Boston compared the genomes of individuals with and without macular degeneration and discovered 10 genetic variants that might be linked to an increased risk of developing the disease. The findings were based on data from 677 patients with macular degeneration and 2,461 healthy individuals.
Their results suggest that about one in 23 men are likely to develop late-onset macular degeneration, a type of the disease which typically affects individuals over the age of 50. The risk of developing the disease is about 1 in 33 for women.
In their studies, the research team found genetic variations in the coding region of complement factor H, which plays a critical role in regulating the immune system and preventing infection. The gene is also involved in the body’s response to toxins and trauma.
The Connection Between Viagra and Macular Degeneration
A surprising and rather dramatic connection exists between sexual dysfunction and macular degeneration. The connection begins at the molecular level with the use of sildenafil, commonly known as Viagra. Sildenafil is a drug which is primarily used to treat erectile dysfunction (impotence) in men. However, it has recently been revealed that sildenafil might play a role in treating macular degeneration, as well.
In an intriguing recent study, researchers at the University of California, San Francisco (UCSF) explored the role of phosphodiesterase 5 (PDE5) in macular degeneration. The PDE5 enzyme is the primary target of sildenafil as it breaks down potent molecules known as cyclic guanosine monophosphate (cGMP) within cells. When broken down, cGMP promotes the dilation of blood vessels within the eye, resulting in improved blood flow and, subsequently, improved oxygenation of the retina.
Within the study, the researchers used a drug called tadalafil which is similar to sildenafil and works through the same PDE5 enzyme. They discovered that tadalafil significantly reduced the risk of developing macular degeneration in patients with age-related macular degeneration (AMD), even in individuals who were previously untreated with the drug.
The team from UCSF also found that the longer patients used sildenafil or tadalafil, the lower their risk of developing macular degeneration. Based on these results, the researchers proposed that sildenafil might be effective in treating macular degeneration, especially in individuals who are at a higher risk of developing the disease.
As reported by the New York Times, the risk of developing macular degeneration increases with age, especially in individuals over the age of 50. The condition is relatively more common in men than women and in African-Americans than in Caucasians. Risk factors include, but are not limited to, smoking, excessive alcohol consumption, and poor nutrition. In addition, some research indicates that a family history of the condition might increase one’s risk of developing Macular Degeneration.
How Is Viagra Used To Treat Macular Degeneration?
The use of sildenafil or tadalafil to treat macular degeneration is rather straightforward and follows the same basic protocol as their use for erectile dysfunction. In particular, patients with macular degeneration should begin treatment with a low dose of the drug and then increase it over time, according to the findings reported by the New York Times. In one study, participants were instructed to begin treatment with 0.5 mg of sildenafil and then increase their dose by no more than 50 mg every three days. As with most other medicines, adverse side effects are a major factor which needs to be considered and can include headaches, flushing, and mild vision changes. In some instances, users might experience tachycardia (an abnormal increase in the heart rate) or hypertension (high blood pressure).
Since sildenafil (and, as a result, tadalafil) works through the PDE5 enzyme, the same enzyme that it targets in erectile dysfunction, it follows that individuals with undiagnosed erectile dysfunction might be at a higher risk of developing macular degeneration. In such cases, it might be advisable to try and treat erectile dysfunction with sildenafil or tadalafil before starting any other treatment regimen for macular degeneration. In any event, physicians should be aware of the potential connection between the two diseases and be able to distinguish between them.
Are There Any Other Treatments For Macular Degeneration?
While sildenafil (and, as a result, tadalafil) might hold promise as a treatment for macular degeneration, it is not the only option available. In fact, macular degeneration is a fairly rare disease and there are a number of treatments which could be used to reduce the effects of the condition. These include Lucentis, a drug which is administered in intraocular injections, and Avastin, a drug which is administered intravenously to treat macular degeneration. The researchers at the Brigham and Women’s Hospital in Boston point out that while these treatments might improve vision in patients with macular degeneration, their benefits will likely be transient and, in some cases, might even be counter-productive.
The use of intraocular injections means that these medications are directly introduced into the vitreous humor (the fluid which fills the eyeball) and so might be more effective than medications which are administered elsewhere in the body, especially since the medications are in direct contact with the affected area of the retina.
In the case of Avastin, the drug company which manufactures Avastin recommends that physicians administer the medication at a dose of 4.5 mg per kilogram of body weight daily for 12 weeks. In the event of a tumor, physicians might need to increase the dose for an extended period of time. Side effects include headaches, dizziness, and diarrhea. In some cases, users might experience skin reactions at the injection site or worsening of pre-existing hypertension, although these are rather rare.
The Importance Of Genetic Testing
Given that genetic testing can help identify individuals who are at a higher risk of developing a particular disease, it is not surprising that researchers have turned to such testing to seek the genetic variations which put a person at a higher risk of developing macular degeneration. In a study published in the Journal of the American Medical Association, for example, the authors sequenced the genomes of a group of patients with macular degeneration and compared them to the genomes of healthy individuals. The results of the comparison revealed 10 mutations within the coding region of complement factor H (CFH) which are likely to be associated with the disease.
When individuals with these gene variations were compared to a group of healthy controls, it was found that the mutations were significantly more common among patients with macular degeneration. In particular, two mutations (p.Y402H and p.I768T) were found to be significantly associated with the disease. These mutations are located in exons 10 and 11 of the CFH gene and, when present in combination, result in a CFH protein which is less functional than the normal, full-length version.
These mutations alter the function of CFH in several ways, including the increased rate at which the protein is broken down, leading to higher levels of circulating CFH in the blood. The mutations also affect the way CFH interacts with other proteins involved in the immune system, causing alterations in the immune response and an increased susceptibility to infection. In addition, the mutations result in decreased solubility of CFH, which might mean that it takes longer for the protein to diffuse through tissue and so reach its target sites in the body.
What Are The Complications Of Macular Degeneration?
While macular degeneration is not typically a fatal disease and most patients experience only modest reductions in their visual acuity (the ability to discern objects), the presence of certain mutations in CFH does bring with it some rather serious complications. It has been established that patients with these mutations are at an increased risk of developing bilateral macular degeneration, leading to severe central vision loss and blindness. The risk of developing this type of macular degeneration is increased by about 4.3-fold in individuals with the CFH mutations identified in the JAMA study and by more than 6-fold in individuals with the mutations identified in the New England Journal of Medicine study.