title: The ocular anomalies in a cystinosis animal model mimic disease pathogenesis.
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.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, France. vasiliki.kalatzis@igmm.cnrs.fr
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kalatzis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serratrice
authors.forename: Claire
authors.initials: C
authors.lastname: Hippert
authors.forename: Olivier
authors.initials: O
authors.lastname: Payet
authors.forename: Carl
authors.initials: C
authors.lastname: Arndt
authors.forename: Chantal
authors.initials: C
authors.lastname: Cazevieille
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Christian
authors.initials: C
authors.lastname: Hamel
authors.forename: François
authors.initials: F
authors.lastname: Malecaze
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Agnes
authors.initials: A
authors.lastname: Müller
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002829:Choroid / Q000378:metabolism / Q000473:pathology; D002924:Ciliary Body / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003545:Cysteine / Q000378:metabolism*; D003554:Cystinosis / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005123:Eye / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005128:Eye Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007429:Intraocular Pressure; D007498:Iris / Q000378:metabolism / Q000473:pathology; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020795:Photophobia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012590:Sclera / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D003545:Cysteine