title: Establishment of a cone photoreceptor transplantation platform based on a novel cone-GFP reporter mouse line.
abstract: We report successful retinal cone enrichment and transplantation using a novel cone-GFP reporter mouse line. Using the putative cone photoreceptor-enriched transcript Coiled-Coil Domain Containing 136 (Ccdc136) GFP-trapped allele, we monitored developmental reporter expression, facilitated the enrichment of cones, and evaluated transplanted GFP-labeled cones in wildtype and retinal degeneration mutant retinas. GFP reporter and endogenous Ccdc136 transcripts exhibit overlapping temporal and spatial expression patterns, both initiated in cone precursors of the embryonic retina and persisting to the adult stage in S and S/M opsin(+) cones as well as rod bipolar cells. The trapped allele does not affect cone function or survival in the adult mutant retina. When comparing the integration of GFP(+) embryonic cones and postnatal Nrl(-/-) 'cods' into retinas of adult wildtype and blind mice, both cell types integrated and exhibited a degree of morphological maturation that was dependent on donor age. These results demonstrate the amenability of the adult retina to cone transplantation using a novel transgenic resource that can advance therapeutic cone transplantation in models of age-related macular degeneration.
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.|Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Smiley
authors.affiliation: Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Nickerson
authors.affiliation: Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
authors.forename: Lacrimioara
authors.initials: L
authors.lastname: Comanita
authors.affiliation: Department of Biochemistry and Molecular Biology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.|Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.affiliation: Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 2J4, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sehemy
authors.affiliation: Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 2J4, Canada.
authors.forename: En Leh Samuel
authors.initials: EL
authors.lastname: Tsai
authors.affiliation: Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 2J4, Canada.
authors.forename: Stuart
authors.initials: S
authors.lastname: Matan-Lithwick
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Sherry
authors.initials: S
authors.lastname: Thurig
authors.affiliation: Department of Biochemistry and Molecular Biology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Touahri
authors.affiliation: Department of Biochemistry and Molecular Biology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dixit
authors.affiliation: Department of Biochemistry and Molecular Biology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.
authors.forename: Tooka
authors.initials: T
authors.lastname: Aavani
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Repentingy
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Baker
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.|Department of Ophthalmology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tsilfidis
authors.affiliation: Department of Comparative Biology and Experimental Medicine, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Biernaskie
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Sauvé
authors.affiliation: Department of Biochemistry and Molecular Biology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.|Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.|Departments of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mears
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.|Department of Ophthalmology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.|Departments of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.|Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 2J4, Canada.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Wallace