Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia. Invest Ophthalmol Vis Sci 2021 Dec 01;62(15):13
Date
12/17/2021Pubmed ID
34913948Pubmed Central ID
PMC8684298DOI
10.1167/iovs.62.15.13Scopus ID
2-s2.0-85122380090 (requires institutional sign-in at Scopus site) 1 CitationAbstract
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.
Author List
Brandt ZJ, Collery RF, Besharse JC, Link BAAuthors
Ross F. Collery PhD Assistant Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinBrian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Genetically Modified
Anti-Infective Agents
Apoptosis
Cell Proliferation
Collagen
Emmetropia
Eye Proteins
Hyperopia
Immunohistochemistry
Macrophages
Membrane Proteins
Metronidazole
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Phenotype
Refraction, Ocular
Sclera
Tomography, Optical Coherence
Zebrafish
Zebrafish Proteins
