title: Impaired vitreous composition and retinal pigment epithelium function in the FoxG1::LRP2 myopic mice.
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.
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cases
authors.affiliation: CNRS, UMR_6270, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University, Mont Saint Aignan F-76821, France; INSERM, U905, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University Hospital, Rouen F-76000, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Obry
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Sirine
authors.initials: S
authors.lastname: Ben-Yacoub
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Augustin
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Plateforme de microscopie électronique, IBPS, UPMC Univ Paris 06, F-75005, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Toutirais
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Simonutti
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, D-13125, Germany.
authors.forename: Annabel
authors.initials: A
authors.lastname: Christ
authors.affiliation: CNRS, UMR_6270, PISSARO Proteomics Platform, Institute for Research and Innovation in Biomedicine, Rouen University, Mont Saint Aignan F-76821, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.affiliation: INSERM, U968, Paris, F-75012, France; UPMC Univ Paris 06, UMR_S968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France. Electronic address: renata.kozyraki@inserm.fr.
authors.forename: Renata
authors.initials: R
authors.lastname: Kozyraki
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009216:Myopia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D009419:Nerve Tissue Proteins; D020727:ADP-Ribosylation Factors; C571368:ARF4 protein, mouse
keywords: Endocytosis; High myopia; Vitreous; low density lipoprotein receptor-related protein 2