title: Cone Genesis Tracing by the Chrnb4-EGFP Mouse Line: Evidences of Cellular Material Fusion after Cone Precursor Transplantation.
abstract: The cone function is essential to mediate high visual acuity, color vision, and daylight vision. Inherited cone dystrophies and age-related macular degeneration affect a substantial percentage of the world population. To identify and isolate the most competent cells for transplantation and integration into the retina, cone tracing during development would be an important added value. To that aim, the Chrnb4-EGFP mouse line was characterized throughout retinogenesis. It revealed a sub-population of early retinal progenitors expressing the reporter gene that is progressively restricted to mature cones during retina development. The presence of the native CHRNB4 protein was confirmed in EGFP-positive cells, and it presents a similar pattern in the human retina. Sub-retinal transplantations of distinct subpopulations of Chrnb4-EGFP-expressing cells revealed the embryonic day 15.5 high-EGFP population the most efficient cells to interact with host retinas to provoke the appearance of EGFP-positive cones in the photoreceptor layer. Importantly, transplantations into the DsRed retinas revealed material exchanges between donor and host retinas, as >80% of transplanted EGFP-positive cones also were DsRed positive. Whether this cell material fusion is of significant therapeutic advantage requires further thorough investigations. The Chrnb4-EGFP mouse line definitely opens new research perspectives in cone genesis and retina repair.
authors.affiliation: Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Decembrini
authors.affiliation: Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Martin
authors.affiliation: Sorbonne Universités, UPMC/Univ Paris 06, UMRS 968, INSERM, U968, Institut de la Vision, 75012 Paris, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.affiliation: Departments of Pediatrics, Ophthalmology and Pharmacology, Hôpital Ste. Justine Research Center, Montreal, QC H3T1C5, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.affiliation: Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Biel
authors.affiliation: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, 8952 Schlieren, Switzerland.
authors.forename: Marijana
authors.initials: M
authors.lastname: Samardzija
authors.affiliation: Pathology Laboratory, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Moulin
authors.affiliation: Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland.
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.affiliation: Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules-Gonin, Fondation asile des aveugles, 1004 Lausanne, Switzerland. Electronic address: yvan.arsenijevic@fa2.ch.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Arsenijevic
mesh_terms: D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012160:Retina / Q000196:embryology / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D047491:Retinoid X Receptor gamma / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D047491:Retinoid X Receptor gamma; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: cones; fusion; neurodegeneration; retina; retinal dystrophy; transplantation