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Joseph C Besharse, Peter Volberding, Brian Link, Ross F Collery; Loss of zebrafish Mfrp causes nanophthalmia and hyperopia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2246. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in human MFRP are associated with nanophthalmia, with extreme shortening of the axial length of the eye resulting in hyperopia. In addition, retinal folding at the macula is often observed, as well as angle closure glaucoma and retinal detachment, the latter likely due to a mismatch between retinal and scleral lengths. Finally, retinas of patients with MFRP mutations exhibit a flecked retinal pathology similar to fundus albipunctatus or Stargardt's disease. Though mutant MFRP orthologs have been identified in mice where they produce retinal flecks demonstrated to be activated macrophages/microglia and photoreceptor degeneration- no animal model has recapitulated the eye axial length shortening or hyperopia phenotypes of human patients.
Zebrafish mfrp was inactivated using CRISPR/Cas9 methods, and eye metrics and refractive state measured using spectral-domain optical coherence tomography. Histology was studied using plastic sectioning and immunohistochemistry.
Zebrafish mfrp-/- mutants show reduced axial length and hyperopia compared to sibling controls. Histological study showed appearance of RPE folding and appearance of subretinal macrophages, which were confirmed by immunohistochemistry.
This zebrafish model of Mfrp-related nanophthalmia and hyperopia will allow detailed study into both the molecular mechanism underlying the retinal degenerative phenotype, macrophage/microglia recruitment and the alterations to eye tissues causing reduced eye size.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
A, B. mfrp-/- adult zebrafish eyes are smaller than wild-type controls as measured by SD-OCT. C, D. RPE folding can be seen in mfrp-/- adult eyes but not in wild-type controls. E, F. Pigmented macrophages are visible subretinally in mfrp-/- adult eyes but not wild-type controls (red arrow).
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