2006 AFAR Research Grant: A Study on the Mechanisms of the Best Vitelliform Macular Dystrophy

Please give a brief summary of your AFAR research project.
Age-related macular degeneration (AMD) is a common disease among the aged population and is a leading cause of blindness in industrialized countries. Since a model for study of AMD is not available at present, the mechanism of AMD remains unknown and effective ways of prevention and treatment of the disease have not been discovered yet.

To reveal the mechanism of AMD, this project will study Best vitelliform macular dystrophy (VMD2) as a model for AMD because there are many similarities between two diseases. VMD2 is caused be mutations of human bestrophin 1 (hBest1) which has been characterized as a Ca-sensitive C1 channel distributed in the basolateral membrane of RPE cells. At present, VMD2 is thought to be a channelopathy. We hypothesize that there probably are common processes in patholocigal mechanisms for both AMD and VMD2 and that VMD2 can be used as a model for AMD study. We believe that clarification of the mechanism of VMD2 will provide important insights in the understanding of AMD.

What problems are you addressing and what specific questions will your research seek to answer?
This study will clarify why the mutations in hBest1 gene can cause the Best vitelliform macular dystrophy. We will answer the question why the disease-causing mutations can lead to loss of ion channel functions of hBest1. Furthermore, the study will provide insight into understanding of age-related macular degeneration mechanism.

What aspects of your project are most interesting from a scientific point of view?
Age-related macular degeneration (AMD) afflicts approximately 20% of the population over the age of 65 years and approximately 35% over 75 in industrialized countries but its mechanism study has been retarded because of lack of a model for its study. If VMD2 disease can be proven to be a model for AMD disease study, the mechanism of AMD will be clarified.

What are the implications of your research for age-related diseases and disorders?
This study aims to find the mechanism of AMD by way of VMD disease as model. Understanding the mechanism of AMD will make the prevention and treatment of AMD possible.

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