title: Fundus autofluorescence (FAF) non-invasively identifies chorioretinal toxicity in a rat model of retinal pigment epithelium (RPE) damage.
abstract: BACKGROUND
  Traditional methods of pre-clinical ocular toxicology require that multiple cohorts of animals be sacrificed over time for terminal histological analysis. By contrast, in vivo techniques capable of following the same cohort prospectively have the potential to be efficient and cost-saving. We therefore asked if fundus autofluorescence (FAF), a non-invasive imaging technique, could detect damage to the posterior pole. Results were compared against electroretinography (ERG), another in vivo technique. The systemic toxin sodium iodate (NaIO3) was used to induce retinal pigment epithelium (RPE) damage.
  
  
  METHODS
  FAF images (488/510nm excitation/emission) were obtained using a commercially available confocal scanning laser ophthalmoscope (cSLO; Heidelberg, HRAII) and were described qualitatively and quantitatively. NaIO3, over a dose range of 5 to 45mg/kg, or saline, was injected via tail vein in 6-10week old Sprague Dawley rats, and FAF images obtained at baseline and days 3, 7 and 14 thereafter and compared against the ERG response amplitude.
  
  
  RESULTS
  Compared against baseline, there was no change in the FAF or ERG responses in the control, 5 or 15mg/kg NaIO3 groups. At 30mg/kg, responses fell into two groups. Half the animals developed small patches of abnormal FAF with modest reductions in the ERG amplitude; the other half developed large areas of damage and had severely reduced ERG responses. At 45mg/kg, all eyes developed extensive areas of abnormal FAF and the ERG was non- or minimally recordable. The en face size of the FAF patches was inversely correlated with the b-wave amplitude.
  
  
  CONCLUSIONS
  This study demonstrates that FAF can detect chorioretinal toxicity in vivo in the rat eye, and that the findings correlate with the ERG. Such in vivo testing can enhance the detection of ocular toxicity.
authors.affiliation: Dept. of Laboratory Medicine & Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3K1, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada.
authors.forename: David Sung Hyeon
authors.initials: DS
authors.lastname: Baek
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Liang
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Dept. of Laboratory Medicine & Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3K1, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada; Dept. of Ophthalmology and Vision Sciences, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3K1, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Pankova
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Dept. of Laboratory Medicine & Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3K1, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5B 1W8, Canada; Dept. of Ophthalmology and Vision Sciences, University of Toronto, 1 King's College Circle, Toronto, ON M5S 3K1, Canada; Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON L8S 4K1, Canada. Electronic address: boyds@smh.ca.
authors.forename: Shelley
authors.initials: S
authors.lastname: Boyd
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005451:Fluorescein Angiography; D007452:Iodates / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000473:pathology*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D007452:Iodates; C032285:sodium iodate
keywords: Biocompatibility; Confocal scanning laser ophthalmoscopy; Fundus autofluorescence; Non-invasive; Rodents; Toxicology