title: Long-term retinal cone survival and delayed alteration of the cone mosaic in a transgenic mouse model of stargardt-like dystrophy (STGD3).
abstract: OBJECTIVE
  To examine the pattern of cone degeneration in the retina of a transgenic mouse model of Stargartd-like dystrophy (STGD3).
  
  
  METHODS
  Investigations were performed on ELOVL4/TG1-2 transgenic (TG) mice and wild-type (WT) littermates from 1 to 24 months of age. Phenotypes were assessed by fundus imaging, fatty acid analysis, and electroretinogram (ERG) recording. Cone degeneration pattern was determined on retina whole mounts using immunohistochemistry and Voronoi domain analyses.
  
  
  RESULTS
  Consistent with low transgene expression, photoreceptors degenerate very slowly. At 1 month, anatomical structure and fatty acid composition of the TG retina is comparable with WT. Rod loss appears at 2 months, exhibiting a central to peripheral gradient, and fundus defects are observed at 3 months. In contrast, cone morphology, distribution and function are still normal at 12 months. Cone loss becomes apparent at 15 months when the outer nuclear layer is reduced to 3 to 4 photoreceptor rows. This process starts at the center of the retina and affects cone subtypes similarly. Very few cones remain at 24 months, after all rods have disappeared (18 months). Quantitative studies focusing on cones expressing M-opsin show a net increase in Voronoi domains and a significant decrease in regularity indexes only beyond 15 months.
  
  
  CONCLUSIONS
  Photoreceptor degeneration in this STGD3 mouse model follows the time course of a slow rod-cone dystrophy. The cone mosaic is preserved for almost 1 year after the onset of rod loss. This long delay provides an opportunity to examine rod-cone interactions during retinal degeneration and to test therapeutic effectiveness at protracting cone dysfunction.
authors: Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors: Sharee
authors: S
authors: Kuny
authors: Marc-André
authors: MA
authors: Filion
authors: Miyoung
authors: M
authors: Suh
authors: Frédéric
authors: F
authors: Gaillard
authors: Yves
authors: Y
authors: Sauvé
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins
keywords: ELOVL4; STGD3; Stargardt-like dystrophy; cone photoreceptor; fatty acids; mouse; retina; secondary degeneration