Age-related macular degeneration treatment in the era of molecular medicine

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The quality of life of both patients and families is impacted by this prevalent disease. Previously, macular degeneration had no known effective treatment. Today, vitamins for non-exudative AMD and intravitreal injection of medications for its exudative form are primary forms of current treatment. Modern advances in molecular science give rise to new possibilities of disease management. In the year 2003 the sequencing of the entire human genome was completed. Since that time, genes such as complement factor H, high-temperature requirement factor A1, and age-relateed maculopathy susceptibility 2 have been discovered and associated with a higher risk of AMD. A patient’s genetic make-up may dictate the effectiveness of current or future therapeutic options. In addition, utilizing genetic data and incorporating it into new treatments (such as viral vectors) may lead to longer-lasting (or permanent) VEGF blockade and specific targeting of complement related genes. There have also been considerable advances in stem cell directed treatment of AMD. Retinal pigment epithelial (RPE) cells can be derived from human embryonic stem cells, induced pluripotent stem cells, or adult human RPE stem cells. Utilizing animal models of RPE and retinal degeneration, stem cell-derived RPE cells have been successfully implanted into the subretinal space. They have been injected as a cell mass or as a pre-prepared monolayer on a thin membrane. Visual recovery has been demonstrated in a retinal dystrophic rat model. Preliminary data on 2 human subjects also demonstrates possible early visual benefit from transplantation of stem cell-derived RPE. As more data is published, and as differentiation and implantation techniques are optimized, the stabilization and possible improvement of vision in individuals with non-exudative macular becomes a real possibility. We conclude that the technologic advances that continue to unfold in both genetic and stem cell research offer optimism in the future treatment of AMD.

Keywords: Age-related macular degeneration, Stem cell therapy, Anti-vascular endothelial growth factor, Gene therapy, Complement factor H, High-temperature requirement factor A1, Age-relateed maculopathy susceptibility 2, Pharmacogenomics, Genetics

Core tip: New therapies for age-related macular degeneration (AMD) such as stem cell transplantation and viral vector delivery are currently under intense investigation. Possible new treatments for both non-exudative and exudative AMD are on the horizon. Human embryonic stem cell derived retinal pigment epithelial cells have been transplanted into the subretinal space in human subjects. Viral vectors that encode proteins with a strong affinity for vascular endothelial growth factor are in clinical trials. In light of these exciting advances in both genetic and stem cell therapy, the future of AMD treatment shows substantial promise.