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Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia
Zachary J Brandt1, Ross F Collery2, Joseph C Besharse2
1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Purpose:
Proper refractive development of the eye, termed emmetropization, is critical for focused vision and is 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 was then used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy were used to further study the eyes.
Results:
Although 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, resulting in a relative refractive error 1.3 times higher than that of non-ablated mfrp siblings.
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 may be recruited in an effort help preserve emmetropization and ameliorate hyperopia.
Insights
Macrophage ablation worsens hyperopia in zebrafish with MFRP gene mutations, indicating these immune cells may help prevent or reduce refractive errors in the eye.
Area of Science:
- Ophthalmology
- Genetics
- Immunology
Background:
- Emmetropization, or proper refractive development, is crucial for clear vision.
- Genetic factors and environmental influences impact emmetropization.
- Mutations in the MFRP gene are linked to congenital hyperopia, characterized by small eyes and short axial length.
Purpose of the Study:
- To investigate the role of macrophages in emmetropization.
- To determine how macrophage depletion affects MFRP-related hyperopia in zebrafish.
Main Methods:
- Utilized a chemically inducible system for cell-specific macrophage ablation in zebrafish.
- Employed spectral-domain optical coherence tomography to measure ocular components and refractive state.
- Conducted histological and electron microscopy analyses to examine eye structure.
Main Results:
- Macrophage ablation did not significantly alter refractive state in wild-type zebrafish.
- Depleting macrophages in MFRP mutant zebrafish significantly worsened their hyperopic phenotype.
- The relative refractive error in ablated MFRP mutants was 1.3 times higher than in non-ablated siblings.
Conclusions:
- MFRP gene inactivation causes hyperopia and retinal macrophage accumulation.
- Ablating macrophages exacerbates MFRP-related hyperopia.
- Macrophages may play a protective role in maintaining emmetropization and mitigating hyperopia.
