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Sci Rep. 2016 Mar 11;6:22867. doi: 10.1038/srep22867.

Establishment of a cone photoreceptor transplantation platform based on a novel cone-GFP reporter mouse line.

Scientific reports

Sheila Smiley, Philip E Nickerson, Lacrimioara Comanita, Narsis Daftarian, Ahmed El-Sehemy, En Leh Samuel Tsai, Stuart Matan-Lithwick, Keqin Yan, Sherry Thurig, Yacine Touahri, Rajiv Dixit, Tooka Aavani, Yves De Repentingy, Adam Baker, Catherine Tsilfidis, Jeff Biernaskie, Yves Sauvé, Carol Schuurmans, Rashmi Kothary, Alan J Mears, Valerie A Wallace

Affiliations

  1. Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada.
  2. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
  3. Division of Vision Science, Department of Ophthalmology and Vision Science, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
  4. 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.
  5. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
  6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 2J4, Canada.
  7. Department of Ophthalmology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
  8. 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.
  9. Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada.
  10. Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
  11. Departments of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

PMID: 26965927 PMCID: PMC4786810 DOI: 10.1038/srep22867

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.

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