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C. Liu, Y. Wang, A. Rattner, J. Nathans, A. Swaroop; Wnt-frizzled Signaling in Retinal Optic Disc Formation and Adult Retina Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1648.
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© ARVO (1962-2015); The Authors (2016-present)
Microphthalmia, coloboma, and persistent fetal vasculature within the vitreous cavity are among the most common human congenital ocular anomalies, and each has been associated with a variety of genetic disorders. Little is known about the role of Wnt-Frizzled signaling in these pathological processes. In mouse, loss of Frizzled5 (Fz5), a Wnt receptor expressed in the developmental optic cup and matured retina - causes all of these defects with high penetrance. Because of variable severity of ocular phenotypes in Fz5 mutants, we hypothesize that other Frizzled receptors may also be involved in maintaining retinal integrity. To address this, we have focused on Frizzled8(Fz8) receptor, which shares high similarity in the extracellular cystein rich domain (CRD) with Fz5, and is also activated by the same Wnt ligand, Wnt9b, in vitro.
A knock-in beta-gal marker was used to investigate Fz8 expression pattern. Fz8 Knockout mice were analyzed for retinal phenotypes. Compound Fz5cko-/-;Fz8-/- knockout mutants are being made for studying functional redundancy of Frizzled receptors. Immunohistology was used to monitor retinal molecular alterations in the mutant mice compared to the wild type.
In Fz8 knockout mutant, ocular development is normal. Frizzled 8 (Fz8) is expressed exclusively in the optic disc in the developing embryonic eye at E14.5. Later, Fz8 expression is observed in multiple retinal cell types. There is an incomplete penetrance of mild persistent fetal vasculature (PFV) phenotype, which is also seen in the Fz5 mutant.
Fz8 and Fz5 may play a redundant role in the development of optic disc. We are examining whether Fz8 may contribute to late onset of retina degeneration because of its expression in Muller glia.
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