title: Evaluation of topical cysteamine therapy in the CTNS(-/-) knockout mouse using in vivo confocal microscopy.
abstract: OBJECTIVE
  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.
authors: Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697-4375, USA. jens@uci.edu
authors: Jennifer L
authors: JL
authors: Simpson
authors: Chyong Jy
authors: CJ
authors: Nien
authors: Kevin J
authors: KJ
authors: Flynn
authors: James V
authors: JV
authors: Jester
mesh_terms: D060433:Administration, Ophthalmic; D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003460:Crystallization; D003543:Cysteamine / Q000008:administration & dosage* / Q000627:therapeutic use; D003553:Cystine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003554:Cystinosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014792:Visual Acuity
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D009883:Ophthalmic Solutions; C534463:cystinosin protein, mouse; D003553:Cystine; D003543:Cysteamine