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Impaired vitreous composition and retinal pigment epithelium function in the FoxG1::LRP2 myopic mice

Item Type:Article
Title:Impaired vitreous composition and retinal pigment epithelium function in the FoxG1::LRP2 myopic mice
Creators Name:Cases, O. and Obry, A. and Ben-Yacoub, S. and Augustin, S. and Joseph, A. and Toutirais, G. and Simonutti, M. and Christ, A. and Cosette, P. and Kozyraki, R.
Abstract:High myopia (HM) is one of the main causes of visual impairment and blindness all over the world and an unsolved medical problem. Persons with HM are predisposed to other eye pathologies such as retinal detachment, myopic retinopathy or glaucomatous optic neuropathy, complications that may at least partly result from the extensive liquefaction of the myopic vitreous gel. To identify the involvement of the liquid vitreous in the pathogenesis of HM we here analyzed the vitreous of the recently described highly myopic low density lipoprotein receptor-related protein 2 (Lrp2)-deficient eyes. Whereas the gel-like fraction was not apparently modified, the volume of the liquid vitreous fraction (LVF) was much higher in the myopic eyes. Biochemical and proteome analysis of the LVF revealed several modifications including a marked decrease of potassium, sodium and chloride, of proteins involved in ocular tissue homeostasis and repair as well as of ADP-ribosylation factor 4 (ARF4), a protein possibly involved in LRP2 trafficking. A small number of proteins, mainly comprising known LRP2 ligands or proteins of the inflammatory response, were over expressed in the mutants. Moreover the morphology of the LRP2-deficient retinal pigment epithelium (RPE) cells was affected and the expression of ARF4 as well as of proteins involved in degradative endocytosis was strongly reduced. Our results support the idea that impairment of the RPE structure and most likely endocytic function may contribute to the vitreal modifications and pathogenesis of HM.
Keywords:High Myopia, Endocytosis, Vitreous, Low Density Lipoprotein Receptor-Related Protein 2, Animals, Mice
Source:Biochimica et Biophysica Acta - Molecular Cell Research
ISSN:0167-4889
Publisher:Elsevier
Volume:1863
Number:6
Page Range:1242-1254
Date:June 2017
Official Publication:https://doi.org/10.1016/j.bbadis.2017.03.022
PubMed:View item in PubMed

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