Novel correlations in cellular, molecular and structural alterations in experimental juvenile myopia

Summary Myopia is a complex and multigenic refractive disorder that does not only impair vision but also increases the risk factor to develop irreversible blinding diseases later in life. While scleral remodeling and decreased connective tissue synthesis have been shown to underly the excessive axial elongation in myopia, the specifics of micro- and macro-level interactions remain elusive. In this proposal, we plan to use tree shrew model of myopia. We hypothesize that infiltration of peripheral immune cells, including myeloid cells correlate with myelin alterations, axonal/neuronal damage ultimately leading to myopia development and progression. We plan to conduct this study in two specific aims. First, we will assess alterations in axonal health, myelin and immune cell infiltration in the optic nerve head (ONH) using immunohistochemical and novel spatial protein profiling by Nanostring in moderate and high myopia. Next, we plan to correlate these micro-level alterations with tissue level alterations from optical coherent tomography (OCT) images of the ONH. We predict that alterations in axonal health, myelin, and inflammation will coincide with the ONH remodeling visualized by OCT in the tree shrew model of myopia. This study will bridge the gap in our understanding of localized molecular mechanisms and pathogenesis involved in ocular remodeling during myopia development. It will ultimately open a whole new avenue towards designing and developing novel treatment strategies that counteract the driving forces of myopia development and progression.