title: Fundus autofluorescence and photoreceptor cell rosettes in mouse models.
abstract: OBJECTIVE
  This study was conducted to study correlations among fundus autofluorescence (AF), RPE lipofuscin accumulation, and photoreceptor cell degeneration and to investigate the structural basis of fundus AF spots.
  
  
  METHODS
  Fundus AF images (55° lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8(-/-)/Abca4(-/-) mice (ages 1-9 months) with a confocal scanning laser ophthalmoscope (cSLO). For quantitative fundus AF (qAF), gray levels (GLs) were calibrated to an internal fluorescence reference. Retinal bisretinoids were measured by quantitative HPLC. Histometric analysis of outer nuclear layer (ONL) thicknesses was performed, and cryostat sections of retina were examined by fluorescence microscopy.
  
  
  RESULTS
  Quantified A2E and qAF intensities increased until age 4 months in the Rdh8(-/-)/Abca4(-/-) mice. The A2E levels declined after 4 months of age, but qAF intensity values continued to rise. The decline in A2E levels in the Rdh8(-/-)/Abca4(-/-) mice paralleled reduced photoreceptor cell viability as reflected in ONL thinning. Hyperautofluorescent puncta in fundus AF images corresponded to photoreceptor cell rosettes in SD-OCT images and histological sections stained with hematoxylin and eosin. The inner segment/outer segment-containing core of the rosette emitted an autofluorescence detected by fluorescence microscopy.
  
  
  CONCLUSIONS
  When neural retina is disordered, AF from photoreceptor cells can contribute to noninvasive fundus AF images. Hyperautofluorescent puncta in fundus AF images are attributable, in at least some cases, to photoreceptor cell rosettes.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Erin
authors.initials: E
authors.lastname: Flynn
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Auran
authors.affiliation: Research Service, Veterans Administration Western New York Healthcare System, Buffalo, New York, United States.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Sullivan
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D008062:Lipofuscin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012162:Retinal Degeneration / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism; D041623:Tomography, Optical Coherence
chemical_list: D008062:Lipofuscin; D012176:Retinoids
keywords: bisretinoid; light; lipofuscin; retina; retinal degeneration; retinal pigment epithelium