EFEMP1 contributes to light-dependent ocular growth in zebrafish

Abstract

Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicatesefemp1in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modifyefemp1expression specifically in the retina of zebrafish. We found that under normal lighting,efemp1mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function.Efemp1modification changed the expression ofefemp1,egr1,tgfb1a,vegfabandrbp3genes in the eye, and changes the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins.Efemp1modification also impacted dark-rearing-induced responses ofvegfabandwnt2bgenes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated byefemp1.SummaryThis study shows that retina-specific modification ofefemp1expression in zebrafish results in myopic eye, and impacts responses to myopia-inducing dark-rearing in eye growth, retinal function, and myopia-associated molecular expression and distribution, implicating light-dependent regulation ofefemp1in ocular development.