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Treatment of corneal cystine crystal accumulation in patients with cystinosis.

Shams F, Livingstone I, Oladiwura D, Ramaesh K - Clin Ophthalmol (2014)

Bottom Line: With increasing age, more severe ocular complications have been reported.Photophobia is a prominent symptom for patients.With prolonged survival and increasing age, this symptom, along with corneal erosions and blepharospasm, can become debilitating.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Gartnavel General Hospital, Glasgow, Scotland.

ABSTRACT
Cystinosis is a rare autosomal recessive disorder characterized by the accumulation of cystine within the cells of different organs. Infantile nephropathic cystinosis is the most common and severe phenotype. With the success of renal transplantation, these patients are now living longer and thus more long-term complications within different organs are becoming apparent. Ophthalmic manifestations range from corneal deposits of cystine crystals to pigmentary retinopathy. With increasing age, more severe ocular complications have been reported. Photophobia is a prominent symptom for patients. With prolonged survival and increasing age, this symptom, along with corneal erosions and blepharospasm, can become debilitating. This review revisits the basic pathogenesis of cystinosis, the ocular manifestations of the disease, and the treatment of corneal crystals.

No MeSH data available.


Related in: MedlinePlus

Mechanism of action of cysteamine.Notes: (A) In normal lysosomes, cystine and other cationic amino acids, such as lysine, freely traverse the membrane. (B) In cystinotic lysosomes, cationic amino acids can freely traverse the membrane, but cystine cannot due to the lack of the transporter cystinosin. Therefore, cystine accumulates inside the lysosome. (C) In cysteamine-treated lysosomes, cysteamine combines with cystine to form the mixed disulfide cysteine–cysteamine, which can use PQLC2, a cationic amino acid transporter, to exit the lysosome, hence reducing the cystine content of the cell.
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f1-opth-8-2077: Mechanism of action of cysteamine.Notes: (A) In normal lysosomes, cystine and other cationic amino acids, such as lysine, freely traverse the membrane. (B) In cystinotic lysosomes, cationic amino acids can freely traverse the membrane, but cystine cannot due to the lack of the transporter cystinosin. Therefore, cystine accumulates inside the lysosome. (C) In cysteamine-treated lysosomes, cysteamine combines with cystine to form the mixed disulfide cysteine–cysteamine, which can use PQLC2, a cationic amino acid transporter, to exit the lysosome, hence reducing the cystine content of the cell.

Mentions: In the 1970s the focus of treatment of cystinosis moved from supportive treatment to therapy, focusing on the lysosomal accumulation of cystine via the oral drug cysteamine. This was first used in the treatment of cystinosis in 1976.10 A cystine-depleting free thiol, cysteamine has been shown to reduce cystine levels both in vitro and in vivo.10 Early treatment with cysteamine has been shown to delay deterioration in renal function, improve growth, and delay nonrenal complications.11 Its mechanism of action is via its entry into the lysosome through a specific transporter, and interaction with cystine, where it forms a cysteamine–cysteine mixed disulfide compound. This compound is then able to exit the lysosome via an intact cationic amino acid transporter.12,13 This transporter, PQLC2, has been shown to be a member of the PQ loop family of proteins, which also includes the cystine carrier protein, cystinosin (Figure 1).14


Treatment of corneal cystine crystal accumulation in patients with cystinosis.

Shams F, Livingstone I, Oladiwura D, Ramaesh K - Clin Ophthalmol (2014)

Mechanism of action of cysteamine.Notes: (A) In normal lysosomes, cystine and other cationic amino acids, such as lysine, freely traverse the membrane. (B) In cystinotic lysosomes, cationic amino acids can freely traverse the membrane, but cystine cannot due to the lack of the transporter cystinosin. Therefore, cystine accumulates inside the lysosome. (C) In cysteamine-treated lysosomes, cysteamine combines with cystine to form the mixed disulfide cysteine–cysteamine, which can use PQLC2, a cationic amino acid transporter, to exit the lysosome, hence reducing the cystine content of the cell.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199850&req=5

f1-opth-8-2077: Mechanism of action of cysteamine.Notes: (A) In normal lysosomes, cystine and other cationic amino acids, such as lysine, freely traverse the membrane. (B) In cystinotic lysosomes, cationic amino acids can freely traverse the membrane, but cystine cannot due to the lack of the transporter cystinosin. Therefore, cystine accumulates inside the lysosome. (C) In cysteamine-treated lysosomes, cysteamine combines with cystine to form the mixed disulfide cysteine–cysteamine, which can use PQLC2, a cationic amino acid transporter, to exit the lysosome, hence reducing the cystine content of the cell.
Mentions: In the 1970s the focus of treatment of cystinosis moved from supportive treatment to therapy, focusing on the lysosomal accumulation of cystine via the oral drug cysteamine. This was first used in the treatment of cystinosis in 1976.10 A cystine-depleting free thiol, cysteamine has been shown to reduce cystine levels both in vitro and in vivo.10 Early treatment with cysteamine has been shown to delay deterioration in renal function, improve growth, and delay nonrenal complications.11 Its mechanism of action is via its entry into the lysosome through a specific transporter, and interaction with cystine, where it forms a cysteamine–cysteine mixed disulfide compound. This compound is then able to exit the lysosome via an intact cationic amino acid transporter.12,13 This transporter, PQLC2, has been shown to be a member of the PQ loop family of proteins, which also includes the cystine carrier protein, cystinosin (Figure 1).14

Bottom Line: With increasing age, more severe ocular complications have been reported.Photophobia is a prominent symptom for patients.With prolonged survival and increasing age, this symptom, along with corneal erosions and blepharospasm, can become debilitating.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Gartnavel General Hospital, Glasgow, Scotland.

ABSTRACT
Cystinosis is a rare autosomal recessive disorder characterized by the accumulation of cystine within the cells of different organs. Infantile nephropathic cystinosis is the most common and severe phenotype. With the success of renal transplantation, these patients are now living longer and thus more long-term complications within different organs are becoming apparent. Ophthalmic manifestations range from corneal deposits of cystine crystals to pigmentary retinopathy. With increasing age, more severe ocular complications have been reported. Photophobia is a prominent symptom for patients. With prolonged survival and increasing age, this symptom, along with corneal erosions and blepharospasm, can become debilitating. This review revisits the basic pathogenesis of cystinosis, the ocular manifestations of the disease, and the treatment of corneal crystals.

No MeSH data available.


Related in: MedlinePlus