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MVRF RESEARCH UPDATE MVRF supports pioneering research on age- related macular degeneration AMD and early onset retinal degenerative diseases that are a major cause of blindness in the world. Specific areas of research include 1 the iden- tification and characterization of genetic mo- lecular and cellular mechanisms underlying retinal degenerative diseases 2 the develop- ment and application of drug gene and stem cell based approaches as treatments to pre- vent or slow vision loss in AMD and early onset inherited retinal degenerative diseases and 3 the design and implementation of state of the artdiagnostic optical imaging techniques. MVRF grant awardees have made significant progress over the past year as indicated in several examples highlighted below. In one study next generation sequencing is being used to identify novel disease-causing mutations in theABCA4 gene associated with Stargardt disease a common early onset macular degeneration associated with severe loss. The identification of novel disease- causing mutations is important for proper genetic counseling and the development of variant-specific therapies for Stargardt disease as we move towards personalized medicine. In another project funded by MVRF a bio- chemical pathway that leads to photore- ceptor cell death is being analyzed at a molecular and cellular level. Myriocin a pharmacological agent known to inhibit a spe- cific step in this pathway has been shown to significantly slow photoreceptor cell death in animal models for retinal degenerative dis- eases. This drug also acts as an anti-inflam- matory agent thereby reducing secondary immune-associated responses which can contribute to the severity of retinal degenera- tive diseases. These studies provide a basis for further evaluating Myriocin in various retinal degenerative diseases includingage-relatedmaculardegeneration. Success in these preclinical studies will lead to future Phase I clinical trials. genetic studies have shown that variants in the complement factor H gene and other complement genes increase ones risk of getting AMD. Suppression of complement activation should prevent or at least slow pho- toreceptor degeneration and loss in vision. In one approach gene therapy is being used to deliver factors which inhibit complement acti- vation in retinal pigment epithelial RPE cells. RPE cells are crucial for photoreceptor sur- vival and play a central role in the ocular im- mune response. Ongoing studies supported by MVRF point to the potential importance of limiting complement activation as a means to reduce photoreceptor cell loss. A potential powerful approach to recover vi- sion in individuals with vision loss from retinal degenerative diseases is to regenerate pho- toreceptors andor retinal pigment epithelial RPE cells. MVRF is funding a number of studies exploring the application of stem cells as a means to regenerate photore- ceptor and RPE cells that are lost as a re- sult of retinal degenerative diseases. In one study in progress efforts are underway to re- program human RPE stem cells into photore- ceptor cells for transplantation. 22 Macula Vision Research Foundation SpringSummer 2015 by Robert S. Molday PhD Director Center for Macular Research University of British Columbia Vancouver BC Chairman MVRF International Scientific Advisory Board