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Foxg1-Cre mediated Lrp2 inactivation in the developing mouse neural retina, ciliary and retinal pigment epithelia models congenital high myopia

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Item Type:Article
Title:Foxg1-Cre mediated Lrp2 inactivation in the developing mouse neural retina, ciliary and retinal pigment epithelia models congenital high myopia
Creators Name:Cases, O. and Joseph, A. and Obry, A. and Santin, M.D. and Ben-Yacoub, S. and Paques, M. and Amsellem-Levera, S. and Bribian, A. and Simonutti, M. and Augustin, S. and Debeir, T. and Sahel, J.A. and Christ, A. and de Castro, F. and Lehericy, S. and Cosette, P. and Kozyraki, R.
Abstract:Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM) is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS) and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5) and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM.
Keywords:Animal Disease Models, Axons, Cell Proliferation, Ciliary Body, Degenerative Myopia, Forkhead Transcription Factors, Genotype, Intraocular Pressure, Knockout Mice, Low Density Lipoprotein Receptor-Related Protein-2, Magnetic Resonance Imaging, Mutation, Nerve Tissue Proteins, Optic Nerve, Phenotype, Prosencephalon, Retina, Retinal Ganglion Cells, Retinal Pigment Epithelium, Sclera, Tramsmission Electron Microscopy, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e0129518
Date:24 June 2015
Official Publication:https://doi.org/10.1371/journal.pone.0129518
PubMed:View item in PubMed

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