Evaluation of topical cysteamine therapy in the CTNS(-/-) knockout mouse using in vivo confocal microscopy.

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  • Author(s): Simpson JL;Simpson JL; Nien CJ; Flynn KJ; Jester JV
  • Source:
    Molecular vision [Mol Vis] 2011; Vol. 17, pp. 2649-54. Date of Electronic Publication: 2011 Oct 08.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Molecular Vision Country of Publication: United States NLM ID: 9605351 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-0535 (Electronic) Linking ISSN: 10900535 NLM ISO Abbreviation: Mol Vis Subsets: MEDLINE
    • Publication Information:
      Original Publication: Atlanta Ga : Molecular Vision, 1995-
    • Subject Terms:
      Amino Acid Transport Systems, Neutral/*deficiency ; Cornea/*metabolism ; Cysteamine/*administration & dosage ; Cystine/*antagonists & inhibitors ; Cystinosis/*drug therapy ; Microscopy, Confocal/*methods; Administration, Ophthalmic ; Amino Acid Transport Systems, Neutral/genetics ; Animals ; Cornea/drug effects ; Cornea/pathology ; Crystallization ; Cysteamine/therapeutic use ; Cystine/metabolism ; Cystinosis/diagnosis ; Cystinosis/metabolism ; Cystinosis/physiopathology ; Disease Models, Animal ; Humans ; Mice ; Mice, Knockout ; Ophthalmic Solutions/administration & dosage ; Ophthalmic Solutions/therapeutic use ; Treatment Outcome ; Visual Acuity
    • Abstract:
      Purpose: The purpose of this study was to assess the ability of quantitative in vivo confocal microscopy (CM) to detect changes in cystine crystal volume in the cystinosisn (Ctns(-/-))mouse cornea following topical cysteamine therapy.
      Methods: Fifteen Ctns(-/-) mice were sequentially followed using in vivo CM from 3 to 10 months of age. In a second experiment, five mice receiving topical cysteamine eyedrops (0.55%) for 4 weeks were compared to five untreated mice. The volume of corneal cystine crystals was determined by thresholding and counting high intensity pixels in the in vivo CM scans and dividing by the stromal volume to calculate a crystal volume index (CVI).
      Results: Corneal crystals progressively increased in density with age, reaching a peak density at 6-8 months and showing a 70 fold increase in CVI. Eyes treated with cysteamine drops showed significantly less crystal accumulation compared to control eyes (p<0.001) with only a 15% increase in treated eyes (p=ns) compared to 173% increase (p<0.04) for untreated eyes.
      Conclusions: Measurement of CVI shows that there is a progressive increase in cystine crystal volume up to 8 months of age and that cysteamine eyedrops significantly inhibits progression in the Ctns(-/-) mouse. These findings are similar to those seen clinically in patients with cystinosis, and suggest that measurement of CVI in the Ctns(-/-) mouse may be used as a model to develop novel therapeutic strategies for treating corneal cystinosis.
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    • Grant Information:
      R24 EY016663 United States EY NEI NIH HHS; EY016663 United States EY NEI NIH HHS
    • Accession Number:
      0 (Amino Acid Transport Systems, Neutral)
      0 (Ophthalmic Solutions)
      0 (cystinosin protein, mouse)
      48TCX9A1VT (Cystine)
      5UX2SD1KE2 (Cysteamine)
    • Publication Date:
      Date Created: 20111109 Date Completed: 20120229 Latest Revision: 20211021
    • Publication Date:
      20231215
    • Accession Number:
      PMC3209421
    • Accession Number:
      22065917