Could One Cause of Macular Degeneration Be a Viral Infection?

The PLoS Pathogens logo. Credit: PLoS Pathogens

Recently, I read a fascinating study in which the researchers have proposed a possible new approach (one of many) to the treatment of age-related macular degeneration, or AMD.

The study, entitled Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization (I will explain/decode!), was published online in the April 2012 issue of PLoS Pathogens, a peer-reviewed open-access journal published monthly by the Public Library of Science (PLoS). The PLoS is a non-profit organization of scientists and physicians who are committed to making the world’s scientific and medical literature a freely available public resource.

The authors are Scott W. Cousins; Diego G. Espinosa-Heidmann; Daniel M. Miller; Simone Pereira-Simon; Eleut P. Hernandez; Hsin Chien; Courtney Meier-Jewett; and Richard D. Dix, representing the following institutions: Duke University Eye Center, Duke Center for Macular Diseases, Department of Ophthalmology; Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine; Department of Biology, Viral Immunology Center, Georgia State University; and the Department of Ophthalmology, Emory University School of Medicine.

Some Terminology to Begin

Here is a brief explanation of the key scientific terms used by the researchers:

  • Murine: related to mice, or using a mouse model in research.
  • Macrophages: specialized cells that attack, ingest, and destroy foreign substances and infectious microbes.
  • Cytomegalovirus: a member of the viral family known as “herpesviruses,” which we know more commonly as “herpes.”
  • Choroidal neovascularization: new (“neo”) blood vessels (“vascularization”) developing in the retina. In wet AMD, abnormal blood vessels begin to grow under the retina. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid, damaging the retina and causing it to lift up and pull away from its base. The choroid is the part of the eye that supplies blood and nutrients to the retina.

About the Study: the Basics

From the Author Summary:

Neovascular age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. Onset of AMD is due to … production of vascular endothelial growth factor (VEGF) that promotes formation of new blood vessels in the retina, thereby leading to retinal tissue destruction and blindness.

Since a [prior] clinical study by us showed that AMD patients have high amounts of antibodies to human cytomegalovirus (HCMV), we [hypothesized] that infection with HCMV might be a risk factor for AMD.

To investigate this possibility, mice were infected with murine [i.e., mouse] cytomegalovirus (MCMV), and at various times after infection, subjected to laser treatment of the eye to induce choroidal neovascularization, an experimental model of AMD.

… chronic human cytomegalovirus (HCMV) infection may … promote AMD by stimulation of VEGF production by activated macrophages [i.e., cells that attack, ingest, and destroy foreign substances and infectious microbes].

Note: Vascular endothelial growth factor (VEGF) is a protein that stimulates abnormal (and damaging) blood vessel growth in the retina and macula. Stopping the growth of these abnormal blood vessels, via anti-VEGF treatments, has been an ongoing development in the treatment of wet AMD.

More about the Research

From an interview with study author Richard D. Dix, via EurekAlert! Science News:

Human cytomegalovirus is a common herpesvirus, said Dix. About 80 percent of the population is estimated to have antibodies for the virus, and it is often acquired during childhood. If a person has a normal, healthy immune system, the virus becomes latent in the cells of bone marrow and blood, he said. But in the elderly, the immune system’s function is reduced, the virus proliferates, and the production of VEGF increases.

Identifying human cytomegalovirus as a co-factor in the development of AMD opens up new paths for the treatment of AMD, Dix said. One route could include reducing the viral load – the amount of the human cytomegalovirus in the blood stream – by treatment with an antiviral drug.

“If we can knock down a certain gene or genes of the virus that stimulates VEGF production, we might be able to decrease its production and minimize AMD,” Dix said.

Conclusions from the Research

From the PLoS article:

We therefore believe that HCMV infection should be considered as a heretofore unrecognized risk factor for development of neovascular AMD…. It is therefore possible that antiviral treatment might be effective in suppressing choroidal neovascularization associated with wet AMD in a fashion similar to that for suppression of … rejection in heart transplant recipients. Future studies will be oriented toward this investigation.

VisionAware will provide updates on this intriguing research as they become available.

Additional sources: dailyRx; EurekAlert!; American Journal of Ophthalmology