Molecular Mechanisms of Emmetropization and Experimental Myopia at Single Cell Resolution

PROJECT SUMMARY More than half of the world’s population is projected to be myopic (nearsighted) by 2050, significantly raising the risk of associated vision-threatening conditions including retinal detachment, maculopathy, and glaucoma. Despite the development of several evidence-based treatments to manage myopia progression, the prevalence and complication rates continue to rise, and treatment efficacy is only partial. Experimental and clinical research shows that complex gene-environment interactions are involved in the control of the post-natal growth of the eye and its optical development, including myopia onset and progression. Research using animal models has confirmed that visual experience and retinal defocus control eye growth and the development of refractive state through the process of emmetropization. While progress has been made uncovering some of the biochemical factors associated with experimental myopia, very little is known about the underlying cellular and molecular mechanisms controlling emmetropization and myopia development. This multi-PI consortium grant brings together experienced researchers and their established experimental non- human primate model of emmetropization and myopia with an internationally recognized ocular genomics research center to perform a major investigation of the retinal, RPE, choroidal, and scleral biology of post-natal eye growth and myopia development. This project examines the functional genomics and gene-environment interactions in the refractive development of the primate eye and will identify molecular mechanisms involved in the development of myopia using single cell and bulk transcriptomics, epigenomics, and proteomics. The investigators will identify and confirm, using established bioinformatic approaches, the main components of key regulatory pathways underlying emmetropization and myopia development. These studies will provide direct evidence and a more complete understanding of the mechanisms of visually regulated eye growth and myopia and will provide the largest and most comprehensive shared resource of cellular and molecular targets to date helping develop new therapies to control eye growth and manage refractive errors. This investigation meets three of the four NEI objectives for myopia research: to investigate the biochemical pathways that regulate eye growth; to identify genes that contribute to the development of refractive errors; and will help develop new technologies for assessing or treating refractive errors.