Cystinosis is an autosomal recessive lysosomal storage disorder in which cystine accumulates within lysosomes due to impairment of the transmembrane lysosomal cystine transporter, cystinosin, encoded by the ubiquitously expressed gene
CTNS.
5,6 Cystine accumulation leads to the formation of cystine crystals within tissues, causing cell death and eventually organ degeneration.
7–10 Kidneys and eyes are the primary tissues impacted by the disease in mice and humans
11,12; Ctns
−/− mice develop ocular pathology similar to humans.
11,13,14 The main ocular manifestation is crystal deposition in the cornea, which begins in infancy, increases with age, and gradually leads to photophobia, blepharospasm, keratopathy, and recurrent corneal erosions.
15 In older patients, filamentous keratopathy, band keratopathy, and peripheral corneal neovascularization also are observed.
15–17 A similar spectrum is seen in the mouse model, with central corneal opacification and loss of the corneal cellular architecture, and eventually phthisis bulbi.
11,13,14,18 Crystals also accumulate in conjunctiva, lens, sclera, ciliary body, iris, trabecular meshwork, choroid, retinal pigment epithelium, and retina, and can cause retinopathy.
19,20 The current treatment for cystinosis is the drug cysteamine, but taken orally it does not improve ocular manifestations of the disease, presumably due to the lack of bioavailability in the cornea.
21 Topical treatment with cysteamine hydrochloride eye drops or a more recent gel formulation is effective in reducing corneal crystal density and alleviating symptoms,
15–17,22–24 but patients still exhibit significant crystal accumulation and associated ocular morbidity, suggesting the need for more potent and durable therapeutics.
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