Ablation ofmpeg+ macrophages exacerbatesmfrp-related hyperopia

Abstract

PURPOSE: Proper refractive development of the eye, termed emmetropization, is critical for focused vision and impacted by both genetic determinants and several visual environment factors. Improper emmetropization caused by genetic variants can lead to congenital hyperopia, which is characterized by small eyes and relatively short ocular axial length. To date variants in only four genes have been firmly associated with human hyperopia, one of which is MFRP. Zebrafish mfrp mutants also have hyperopia and similar to reports in mice, exhibit increased macrophage recruitment to the retina. The goal of this research was to examine the effects of macrophage ablation on emmetropization and mfrp-related hyperopia. METHODS: We utilized a chemically inducible, cell-specific ablation system to deplete macrophages in both wild-type and mfrp mutant zebrafish. Spectral-domain optical coherence tomography (SD-OCT) was used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy was used to further study the eyes. RESULTS: While macrophage ablation does not cause significant changes to the relative refractive state of wild-type zebrafish, macrophage ablation in mfrp mutants significantly exacerbates their hyperopic phenotype. CONCLUSIONS: Genetic inactivation of mfrp leads to hyperopia as well as abnormal accumulation of macrophages in the retina. Ablation of the mpeg1-positive macrophage population exacerbates the hyperopia, suggesting that macrophages are recruited in an effort help preserve emmetropization and ameliorate hyperopia.