PROJECT SUMMARY/ABSTRACT Our proposed research will utilize tissue generated from funded studies and employ transcriptomics and proteomics to precisely characterize how the sclera is affected in myopia, directly addressing several objectives of the NEI’s strategic plan regarding the “from genes to disease mechanisms” area of emphasis. This supplement proposal addresses a missed opportunity in our funded work that can be addressed with much of the current resources, providing the first comprehensive cellular and molecular dataset for rhesus monkey ocular structures to aid in the development of novel therapies for myopia. For reasons not well understood, a significant and rapidly increasing proportion of the population develops myopia, or nearsightedness. Because of structural changes that take place as the eye becomes myopic, even low degrees of myopia pose a significant risk for numerous blinding conditions. Myopia is now one of the leading causes of permanent visual impairment in the world and represents a substantial economic burden. Billions of dollars are spent annually on optical corrections and pathologies caused by myopia. The long-term goal of our research program is to provide a better understanding of the etiology of the most common form of myopia, juvenile-onset myopia, and to develop effective treatment strategies that reduce the burden of myopia. Little is known about transcriptomic and other phenotypic changes in the primate sclera, which limits the ability to develop novel treatments and translate these towards clinical practice. Since fibroblasts, the primary cell type in sclera, mediate the scleral remodeling that ultimately leads to myopic axial ocular elongation, this fundamental knowledge gap also hinders development of scleral fibroblast- centric molecular interventions for preventing myopia. Our findings will provide a comprehensive foundation for examining scleral mechanisms during myopia and have the potential to identify novel scleral targets to treat myopia in children. Our purpose is to generate knowledge that can be applied to the human eye; however, many of the required experiments cannot be conducted in humans. Therefore, these experiments will be conducted using non-human primates. Here, controlled rearing strategies, rigorous optical and biometric measurements and molecular techniques, including single cell sequencing, will be used to determine: 1) which cell types in the sclera respond to experimental myopia and 2) molecular changes in the extracellular matrix of sclera in response to experimental myopia. Our study combines many approaches across different disciplines (genomics, cell and molecular biology, and mass spectrometry) to produce the most complete description of scleral changes in myopia. Results of these studies will potentially provide the scientific foundation for novel treatment and management strategies for the most common forms of myopia in children to prevent and slow the progression of myopia, in...