Mucopolysaccharidosis (MPS) in ocular tissues as induced by amphiphilic di-cationic drugs.
The immunostimulatory drug tilorone (2,7-bis(2- (diethylamino)ethoxy)-9H-fluorene-9-one) has previously been described to induce keratopathy in patients and in rats; in the latter, lysosomal storage of sulfated glycosaminoglycans (mucopolysaccharidosis, MPS) was found to be the reason for corneal clouding. In the present histochemical and ultrastructural study, several ocular tissues of rats were examined after chronic treatment with tilorone and two other immunostimulatory agents (3,6-bis(2-(dipiperidyl)ethoxy)-acridine and the diethylamino analogue). The acridine derivatives hardly affected the cornea and sclera. Tilorone as well as the acridine derivatives induced significant MPS in ciliary body, iris, and choroid. While the functional consequences of drug-induced MPS in ocular tissues are not known yet, except for the cornea, this adverse drug action should be taken into account when new compounds are designed that share certain physicochemical features with tilorone. One molecular feature essential for the MPS-inducing potency of a drug appears to be the dicationic amphiphilic character.
Lüllmann-Rauch
R
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Department of Anatomy, University of Kiel, Germany.
D000166:Acridines / Q000633:toxicity*; D000818:Animals; D003228:Conjunctiva / Q000187:drug effects / Q000648:ultrastructure; D003315:Cornea / Q000187:drug effects / Q000648:ultrastructure; D005123:Eye / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D009083:Mucopolysaccharidoses / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012590:Sclera / Q000187:drug effects / Q000648:ultrastructure; D013994:Tilorone / Q000633:toxicity*; D014602:Uvea / Q000187:drug effects / Q000648:ultrastructure
D000166:Acridines; C045570:3,6-bis(2-piperidinoethoxy)acridine trihydrochloride; D013994:Tilorone