RECENT RESEARCH HIGHLIGHTS
Significant advancements have been made in understanding the underlying causes of age-related macular degeneration (AMD) and early onset inherited retinal degenerative diseases. AMD is a leading cause of vision loss in people over the age of 50 affecting over 50 million people worldwide. It is caused by the interplay of genetic, environmental and lifestyle risk factors. An international effort has led to the identification of the most common genetic variants that contribute to one’s risk of developing AMD. These variants have been broadly associated with ocular inflammation and oxidative stress that can cause the destruction of retinal pigment epithelial (RPE) cells in the central (macula) region of the retina and as a consequence the death of photoreceptor cells and the loss in vision. A number of studies, some of which are supported by MVRF, have focused on developing RPE cells and photoreceptor cells from stem cells for retinal transplantation. Although still early in its development, several clinical trials have been initiated to determine if transplantation of stem cell derived RPE cells is safe and can restore vision or at least slow or prevent further vision loss in individuals with AMD and Stargardt disease, an early onset inherited macular degeneration. Transplantation of photoreceptors is a more challenging problem, but steady progress is being made in developing appropriate cells for transplantation into animal models for retinal diseases.
In another area of study supported by MVRF, scientists are using gene therapy to restore vision in individuals with inherited retinal degenerative diseases. Earlier studies have shown that viral-mediated delivery of the RPE65 gene to individuals with a severe retinal degenerative disease known as Lebers Congenital Amaurosis (LCA) is safe and partially restores vision. Gene therapy has also been successfully used to restore vision and sustain photoreceptor cell survival in animal models for a number of inherited retinal degenerative diseases. These pioneering studies have now led to the initiation of new gene therapy clinical trials for a number of genetic eye diseases.
In another important area of study, researchers have developed a technology known as Crispr/Cas9 that has the power of editing existing genes. This method is now widely used to edit genes in cells grown in culture. As the technology matures, it has the potential of correcting defective genes in RPE and photoreceptors of animal models and eventually human with known retinal diseases.
The application of drug-based therapy is also under intense investigation as treatment for retinal diseases. Ranibizumab (trade name Lucentis) and bevacizumab (trade name Avastin), two related compounds that blocks the growth of abnormal blood vessels in the macula, have been shown to slow vision loss and in some cases improve visual acuity in individuals with the wet form of AMD. A number of new drugs are now being developed to further improve the outcome of individuals with the wet and dry form of AMD. Pharmaceutical agents are also being developed that target specific biochemical pathways associated with retinal degenerative diseases. Drug therapy may be particular useful in combination with other types of therapy including stem cell and gene therapy.
Finally in another area of MVRF supported investigation, research teams are developing new and improved instruments to image the retina. In one example adaptive optics which has been widely used in astronomy to correct for optical distortions is now being improved to image individual rod and cone photoreceptors at high resolution. Such instruments are important for monitoring disease progression and evaluating the effect of therapeutic interventions on photoreceptor cells.
These and other studies have greatly contributed to our understanding of retinal diseases. Translation of this knowledge into promising therapeutic interventions is proceeding at an ever increasing rate. With continued funding, there is optimism that treatments and cures for AMD and other diseases will be developed in the not too distant future that will benefit affected individuals.
GENE THERAPY PROGRESS