title: Dose-dependent retinal changes following sodium iodate administration: application of spectral-domain optical coherence tomography for monitoring of retinal injury and endogenous regeneration.
abstract: BACKGROUND
  The purpose of this study was to demonstrate the progression of acute retinal injury by correlating histological sections with in vivo spectral-domain optical coherence tomography (SD-OCT) images.
  
  
  METHODS
  Male C57BL/6 mice were treated intravenously with two different sodium iodate (NaIO3) doses (35 mg/kg or 15 mg/kg). In vivo SD-OCT was performed up to 3 months post-injury. Ex vivo retinal histology, TUNEL and IsolectinB4 immunostaining were also conducted. Quantitative comparison of histopathological images and SD-OCT images was performed.
  
  
  RESULTS
  SD-OCT examination revealed that administration of 35 mg/kg NaIO3 was associated with progressive and irreversible retinal degeneration. On day 3 post-injury, we found numerous apoptotic cells in the outer nuclear layer (ONL) that strongly corresponded to hyper-reflective areas in the SD-OCT images. At 7 d post-injury, SD-OCT images showed irregular-shaped patterns of hyper-reflectivity in the retinal pigment epithelium (RPE) that corresponded with the accumulation of macrophages phagocytosing melanin granules and cell debris. Additionally, we documented hyper-reflective opacities in the vitreous that were most numerous at 7 d. At 3 months post-injury, the neurosensory retina was significantly thinner, predominantly due to progressive photoreceptor (PR) loss. In contrast, administration of 15 mg/kg NaIO3 did not induce hyper-reflectivity of ONL in SD-OCT images, which indicates a lack of massive PR cell death. At 3 months post-injury, SD-OCT images showed the complete restoration of outer retina lamination and restoration of hyper-reflective structural bands. Histological assessment of retinas acquired after the last SD-OCT imaging session revealed complete regeneration of the RPE and considerable improvement of PR architecture.
  
  
  CONCLUSIONS
  Our findings showed the high level of effectiveness of SD-OCT imaging for monitoring dynamic changes in retinal morphology following acute retinal injury. Moreover, we demonstrated for the first time that SD-OCT can be used to non-invasively detect regeneration in the damaged retina.
authors.affiliation: Department of Histology and Embryology .
authors.forename: Anna
authors.initials: A
authors.lastname: Machalińska
authors.forename: Renata
authors.initials: R
authors.lastname: Lejkowska
authors.forename: Michał
authors.initials: M
authors.lastname: Duchnik
authors.forename: Miłosz
authors.initials: M
authors.lastname: Kawa
authors.forename: Dorota
authors.initials: D
authors.lastname: Rogińska
authors.forename: Barbara
authors.initials: B
authors.lastname: Wiszniewska
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007452:Iodates / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000473:pathology; D012038:Regeneration / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D006023:Glycoproteins; D007452:Iodates; C473590:isolectin B4-binding glycoprotein, mouse; C032285:sodium iodate
keywords: Cell death; histology; optical coherence tomography; regeneration; sodium iodate