The ocular anomalies in a cystinosis animal model mimic disease pathogenesis.
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.
Kalatzis
Vasiliki
V
Institut de Génétique Moléculaire de Montpellier, France. vasiliki.kalatzis@igmm.cnrs.fr
Serratrice
Nicolas
N
Hippert
Claire
C
Payet
Olivier
O
Arndt
Carl
C
Cazevieille
Chantal
C
Maurice
Tangui
T
Hamel
Christian
C
Malecaze
François
F
Antignac
Corinne
C
Müller
Agnes
A
Kremer
Eric J
EJ
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
D026921:Amino Acid Transport Systems, Neutral; D003545:Cysteine