Myopia causes serious social problems in China. Our primary interest is myopia pathogenesis and clinical intervention research. We elucidate the mechanism of myopia in the organization, cell and molecular level through drug intervention, gene knockout and single cell sequencing and other new and effective means of research.

We first established platforms for measuring refraction and axial length in mice eyes enabling him to ultimately show that mice are a feasible experimental model for myopia. We then identified that i, scleral hypoxia is the triggering factor for extracellular matrix (ECM) remodeling and axial elongation in myopia (seen the following Fig. 1), ii decrease in choroidal blood flow causes scleral hypoxia, iii, abnormal visual input can induce myopia by disrupting the homeostasis between retinal dopamine D1 and D2 receptor subtypes (seen the following Fig. 1). The applicant has thus proposed a comprehensive working model of myopia: risk factors such as near-work can disrupt the homeostasis between retinal dopamine D1 and D2 receptor subtypes, which cause a decrease in choroidal blood flow resulting in scleral hypoxia, followed by scleral ECM remodeling and finally myopia occurs. Our hypothesis of sclera hypoxia (seen the following Fig. 1) was thought to be one of the major milestones in the history of myopia research

Fig. 1. Hypothesis of sclera hypoxia underlying myopia development（近视形成的巩膜缺氧学说）(A) The choroidal layer thins rapidly followed by scleral thinning that results from ECM remodeling during myopic visual stimulus. (B) These myopia-related visual signals decrease choroidal blood flow that leads to an insufficient supply of oxygen and nutrients to the avascular sclera. Scleral fibroblasts first sense and quickly respond to the altered extracellular microenvironment through the accumulation of HIF-1α and enhanced phosphorylation levels of eIF2α and mTOR. This induces a phenotypic shift of fibroblast-like cells toward myofibroblast-like cells as well as a decrease in collagen production. As a result, the sclera becomes thinner and weaker. Consequently, axial length increases, and myopia ensues. (Figure 7 in Wu H, et al. Proc Natl Acad Sci U S A. 2018.)

 

Fig. 2. A working hypothesis: Homeostatic control of myopia by opposing effects of D1-like and D2-like receptors in mouse eye. Based on genetic and pharmacological results from mouse models of myopia, we postulate that D1-like and D2-like receptor activation in distinct cell types exert homeostatic control of the emmetropization process. The balance of D1-like and D2-like receptor activation in the eye modulates refractive eye development, such that over activation of D1-like receptors leads to hyperopia while over activation of D2-like receptors leads to myopia. (Figure 1 in Zhou X, et al. Prog Retin Eye Res. 2017).