Abstract
Cystinosis is a lysosomal storage disorder characterized by abnormal accumulation of cystine, which forms crystals at high concentrations. The causative gene CTNS encodes cystinosin, the lysosomal cystine transporter. The eye is one of the first organs affected (corneal lesions and photophobia in the first and visual impairment in the second decade of life). We characterized the ocular anomalies of Ctns−/− mice to determine whether they mimic those of patients. The most dramatic cystine accumulation was seen in the iris, ciliary body, and cornea of Ctns−/− mice. Consistently, Ctns−/− mice had a low intraocular pressure (IOP) and seemed mildly photophobic. Retinal cystine levels were elevated but increased less dramatically with age. Consistently, the retina was intact and electroretinogram (ERG) profiles were normal in mice younger than 19 mo; beyond this age, retinal crystals and lesions appeared. Finally, the lens contained the lowest cystine levels and crystals were not seen. The temporospatial pattern of cystine accumulation in Ctns−/− mice parallels that of patients and validates the mice as a model for the ocular anomalies of cystinosis. This work is a prerequisite step to the testing of novel ocular cystine-depleting therapies.
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Abbreviations
- ERG:
-
electroretinogram
- IOP:
-
intraocular pressure
- RPE:
-
retinal pigment epithelium
- TEM:
-
transmission electron microscopy
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Acknowledgements
The authors thank the IGMM animal house staff for their indispensable help, M. Villain for helpful discussions, C. Depeyre and G. Dubois for technical help, and the Montpellier RIO Imaging platform and CRIC for light and TEM facilities, respectively.
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This project was funded by the Association Française contre les Myopathies (France) and the Cystinosis Research Network.
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Kalatzis, V., Serratrice, N., Hippert, C. et al. The Ocular Anomalies in a Cystinosis Animal Model Mimic Disease Pathogenesis. Pediatr Res 62, 156–162 (2007). https://doi.org/10.1203/PDR.0b013e31809fda89
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DOI: https://doi.org/10.1203/PDR.0b013e31809fda89
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