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Michael Zuber, Galina Bachay, Reyna Martinez-De Luna, William J Brunken, Andrea Sophia Viczian; Severe retinal dysplasia and detachment in mice lacking Maturin. Invest. Ophthalmol. Vis. Sci. 2017;58(8):108.
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© ARVO (1962-2015); The Authors (2016-present)
We originally identified Maturin in a screen for genes required for normal eye formation. Knockdown of Maturin in the Xenopus laevis neural plate blocks cell cycle exit, while overexpression drives neurogenesis. Maturin has been highly conserved through evolution and is expressed in the developing X. laevis and mouse eye. The purpose of this study was to determine if Maturin loss alters retinal neurogenesis during mammalian eye formation.
The effect of Maturin loss on retinal histogenesis was determined by comparing the postnatal retinal development of wild-type animals and Maturin null mice using histology and immunohistochemistry.
The postnatal consequence of Maturin loss was retinal dysplasia. In mild cases, dysplasia manifest as a localized thickening of the retinal layers. In severe cases, dysplasia resulted in buckling of the retina to form multiple folds sometimes extending through half of a retinal section, and resulted in detachment from the RPE. Finger-like projections were also observed, which formed retinal tubes that extended into the vitreous, then folded back onto the retina proper. Immunohistochemistry to detect photoreceptors, inner nuclear and retinal ganglion cells indicates retinal cell types differentiated and are positioned in the expected retinal layers - even in areas where retinal dysplasia is severe. Calretinin is expressed in the soma and processes of amacrine and retinal ganglion cells, which synapse on bipolar cells in the inner plexiform layer. In controls, calretinin-positive projections form three distinct synaptic layers in the inner plexiform layer. Although calretinin-positive processes were present, synaptic layers were disrupted in dysplastic regions of retinas lacking Maturin. Dysplasia was detected in animals as young as P22 and as old as 13 months.
Maturin is required for normal retinal neurogenesis during mouse eye development. In X. laevis, Maturin is required for normal cell cycle exit and neural differentiation. Therefore, our working hypothesis is that the dysplasia observed in mice lacking Maturin is due to excessive proliferation of retinal progenitor cells during retinal histogenesis. Experiments to determine the mechanism and if the additional cells are generated pre- and/or post-natal are in progress.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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