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.

Grant Number: 5R21EY036560-02
NIH Institute/Center: NIH
Principal Investigator: PRIYA CHAUDHARY